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Oxadiazole in Medicine and Drug Discovery 153
fused with triazolo and tetrazolo groups, and pyrazine was created. The synthesized
compounds were evaluated for in vitro antitubercular activity against MTB H37Rv,
using isoniazid and RIF as reference medications. With a MIC of 6.25 to 50 ȝJ/ml,
the compound demonstrated strong antitubercular action against MTB H37Rv (Das
et al. 2015). A series of new 1,3,4 oxadiazole-containing quinoline motifs as possible
DQWLWXEHUFXODU GUXJV 8VLQJ WKH /RZHQVWHLQ-HQVHQ PHGLXP WKH GHULYDWLYHV ZHUH
tested for MTB H37Rv resistance using RIF and isoniazid as reference medicines.
At a 250 ȝJ/ml dosage, four compounds were determined to be the most effective
in the main screening, inhibiting MTB H37Rv by more than 90%. The MIC values
of the active hybrids ranged from 0.060 to 0.223 mM (Ladani et al. 2015). As
possible antitubercular drugs, pyrazine containing 1,3,4 oxadiazoles synthesized
and combined with substituted azetidin-2-ones. The synthesized compounds
were tested for in vitro antitubercular activity against MTB H37Rv using the
/RZHQVWHLQ-HQVHQ DJDU PHWKRG DQG LVRQLD]LG DQG 5,) ZHUH XVHG DV UHIHUHQFH
medications. With a MIC value of 3.12 g/ml, the synthesized compounds were
discovered to be the most effective against MTB H37Rv. The antitubercular
potential of the compound was moderate (MIC = 6.25 g/ml). High docking scores
for compounds were in the range of 69.449 and 64.705 (Das and Mehta 2015). Novel
pyrazole-oxadiazole hybrids were synthesized as possible antitubercular drugs,
exhibiting MICs of 0.92–2.56 ȝJ/ml against MTB H37Ra in the active state. With
MICs between 0.79 and 2.71 ȝJ/ml, compounds showed substantial efficacy against
M. bovis BCG in the active form. The compounds were successfully docked into the
active site of mycobacterial enoyl reductase, according to docking studies (InhA),
with a binding energy of 66.459 kcal/mol and a docking score of 10.366 (Desai
et al. 2022a). Desai and co-workers synthesized furan and pyridine-based oxadiazole
hybrids as possible antitubercular drugs. When tested against MTB H37Ra and
M. bovis BCG, it showed outstanding antitubercular activity within the range of
97.09 to 98.66% inhibition at a concentration of 30 ȝJ/ml. The molecules were
successfully docked into the active site of mycobacterial enoyl reductase, according
to a docking study (InhA), with a binding energy of 49.893 kcal/mol and a docking
score of 8.991, respectively (Desai et al. 2022a).
2[DGLD]ROH,QGROH3\ULGLQH%HQ]RWKLD]ROHDQG
Benzoimidazole Conjugates
Researchers are interested in studying the synthesis and pharmacological properties
of pyridine heterocycles because of their biological significance and pharmacological
and medical potential. Pyridine has a wide range of biological effects, including
anticancer, antimicrobial, anticonvulsant (Prasanthi et al. 2014), antibacterial
)URORYD HW DO DQWLLQIODPPDWRU\ %UXQ HW DO DQG DQWLWXPRU -LDR
et al. 2015) properties. The nitrogen heterocycle with the pyridine moiety is
most likely found throughout nature. Tryptophan, an amino acid, and serotonin,
a neurotransmitter, both contain indole moiety as a necessary component. Indole
scaffolds display biological activities which are demonstrated by compounds with
a 1,3,4-oxadiazole ring (Desai et al. 2018). By using the XTT reduction menadione
assay and the nitrate reductase assay, the indole and pyridine-based 1,3,4 oxadiazole
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154 Oxadiazole in Material and Medicinal Chemistry
compounds against M. bovis BCG and MTB H37Ra have been developed and
tested for their in vitro antitubercular efficacy. RIF and isoniazid were considered
as controls. In vitro tests of different synthetic compounds against M. bovis BCG
in both active and dormant states showed potent antitubercular activity. In contrast,
other compounds were shown to have excellent antitubercular activity against
M. bovis BCG in both the active (0.94–5.17 ȝJ/ml) and dormant states
(0.85–4.97 ȝJ/ml), respectively. Many other compounds were subjected to a
molecular docking study against mycobacterial enoyl reductase (PDB code: 4TZK),
which revealed information about the thermodynamic interactions and binding mode
with the highest GLIDE docking score, which ranged from 8.07 to 8.267 (Desai
et al. 2016). In order to test for in vitro antitubercular activity against MTB H37Rv,
the benzimidazolyl 1,3,4-oxadiazol 2ylthio-Nphenyl (benzothiazolyl) acetamides
were synthesized. The compound showed excellent inhibition activity with a MIC
value of 6.25 ȝJ/ml from BACTEC MGIT, a compound with a methoxy group at the
para position to the N phenyl acetamide moiety, exhibiting excellent antitubercular
DFWLYLW\7KH/RZHQVWHLQ-HQVHQ0,&PHWKRGZDVXVHGWRVFUHHQWKHVHFRPSRXQGV
which displayed MIC values of 12.5 ȝJ/ml, representing their antitubercular potency
(Patel et al. 2012).
3. Applications
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Mycobacterium tuberculosis (MTB), a deadly pathogen that kills more people than
any other microbial species, is the cause of tuberculosis (TB). This was first discovered
by Robert Koch in 1882. It is the second-leading cause of death, behind COVID-19
(behind HIV/AIDS) (WHO Report 2024). Other microbial species related to MTB,
such as Mycobacterium avium and Mycobacterium africanum, can also cause TB
(Beena and Rawat 2013). About 75% of active TB cases are pulmonary TB, while
the remaining cases are extrapulmonary TB, in which the bacteria affect the bones,
pleura, joints, and lymphatic system (Rivers and Mancera 2008). The World Health
Organization (WHO) estimates that 1.5 million people will die worldwide from
tuberculosis (TB) in 2020. In the same year, there were 10.0 million new cases of TB
worldwide (WHO Report 2021). The first antitubercular drug to be discovered was
streptomycin, and its first extensive clinical trial was carried out in 1948, followed by
thioacetazone and para-aminosalicylic acid as the potential antitubercular drugs (A
Medical Research Council Investigation 1950; Keshavjee and Farmer 2012). High
curability rates and decreased susceptibility to antibiotic resistance were produced
by combining the two medications (Crofton and Mitchison 1948). However, the
widespread emergence of streptomycin drug resistance fueled the creation, research,
and development of fresh anti-TB medications (Azevedo and Robinson 2015). These
include cycloserine, ethionamide, PZA, rifampicin (RIF), ethambutol, and isonicotinic
acid (isoniazid INH). Even though TB is treatable, it still has a high mortality rate
and is the most contagious illness in the world. Inadequate case detection remains a
significant issue for TB infection control despite the development and expansion of
directly observed treatment, short-course programs, and the increased success rate of
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Oxadiazole in Medicine and Drug Discovery 155
therapy (Keshavjee and Farmer 2012). Due to the emergence of drug-resistant strains,
TB has now become a serious issue. Drug-resistant strains led to the development of
both extensive drug-resistant TB (XDR-TB) and multidrug-resistant TB (MDR-TB).
While XDR-TB is resistant to any antibiotic, including capreomycin, kanamycin, and
amikacin, MDR-TB is resistant to isoniazid and RIF (Caminero and Sotgiu 2010).
It is urgently necessary to create hybrid molecules by fusing two or more bioactive
heterocyclic moieties into a single molecular scaffold to combat the issue of MDR
and TDR TB. To create new hybrids with antitubercular properties, the compounds
II, 2 heptadecyl 5 (pyridine 4 yl)1,3,4 oxadiazole, and I, 2 pentadecyl 5 (pyridine
4 yl)1,3,4 oxadiazole, were chosen as two active hybrids against M. bovis. These
hybrids have antitubercular properties against M. bovis with respective minimum
inhibitory concentrations (MICs) of 0.35 and 0.65 ȝ0 1DYDUUHWHဨ9i]TXH] HW DO
2007). The emergence of strains that are both multi- and totally drug-resistant has
made it necessary to look for more potent molecules to combat microbial species like
MTB, which is both multi- and totally drug-resistant.
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Each year, more than 229 million malaria cases are discovered (WHO Report 2021).
More than one hundred countries still experience malaria, which is still a serious
health concern in Africa and Asia (Wilkerson et al. 2021). The parasites that caused
malaria developed asexually in the host and were spread by female anopheles
mosquitoes (Cowman et al. 2016). Plasmodium falciparum, along with Plasmodium
falciparum, Plasmodium malariae, Plasmodium vivax, Plasmodium ovale, and
Plasmodium knowlesi is the most dangerous species among all the parasites that
cause malaria in humans.
The pyrazole acrylic acid-based oxadiazole derivatives were synthesized,
which showed in vitro antimalarial activity using a culture of the P. falciparum
chloroquine-sensitive strain. To the chloroquine-sensitive and chloroquine-resistant
strains of P. falciparum, the compound showed between 0.245 and 0.724 ȝJ/ml.
According to molecular docking studies, compounds had docking scores of 5.309 to
6.844, respectively (Verma et al. 2018). Verma and co-workers prepared and tested
a series of pyrazole-clubbed oxadiazoles for antimalarial activity. The antimalarial
screening results against P. falciparum, which is sensitive to chloroquine, indicated
the potential for the antimalarial agents with a value of 0.886, 0.248, 0.647, 0.322,
0.582, and 0.494 ȝJ/ml. The catalytic domain of falcipain was shown to interact
through hydrogen bonding in the molecular docking study, which resulted in a
docking score of 5.532 (Verma et al. 2019). Novel 1,3,4-oxadiazole analogs were
synthesized, showing that antibacterial and antimalarial activities in vitro are quite
effective against P. falciparum pathogen. Both pyrimethamine and chloroquine were
used as common medications. The potential as a DHFR inhibitor with a binding
energy of 7.20 kcal/mol was disclosed by a molecular docking analysis against
P. falciparum dihydrofolate reductase, which revealed contact with the active
site (amino acids) of the receptor (Thakkar et al. 2017). The crystal structure,
density functional theory, quantum theory of atoms in molecules, and hybrid
quantum mechanics/molecular mechanics binding energy analysis were studied
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156 Oxadiazole in Material and Medicinal Chemistry
(Al-Wahaibi et al. 2019) to investigate the potential antimalarial lead candidate
2(4-fluorobenzylthio)5-(5-bromothiophen-2-yl)1,3,4-oxadiazole 95. By blocking the
DHFR target with a Glide XP score of less than 5.4 kcal/mol, the molecule may be
a viable antimalarial lead candidate, according to the in-silico analysis of PfDHFR.
$QWLఆ,QIODPPDWRU\$FWLYLW\
The body’s complicated biochemical response to irritants, infections, damaged
cells, and other stimuli is inflammation. Inflammation can be acute or persistent.
Numerous illnesses, including hay fever, periodontal disease, atherosclerosis,
and osteoarthritis, are linked to chronic inflammation. The manufacture of
pro-inflammatory prostaglandins from arachidonic acid results in inflammation
(Smith et al. 1998; Warner et al. 1999). Biosynthesis involves the cyclooxygenase
(COX) enzyme; prostaglandins are produced into pro-inflammatory prostaglandins,
which are then released into tissues to cause inflammation. Cyclooxygenase 1
(COX1) and cyclooxygenase 2 (COX2) are the two isoforms of the COX enzyme.
The overproduction of prostaglandins during inflammation is caused by COX-2
(Srivastava et al. 2003). Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve
pain, fever, and inflammation when used in greater quantities, they also prevent
blood clots (Palomer et al. 2002; Merry et al. 2010). Depending on the medication,
side effects can include an increased risk of stomach ulcers and bleeding, heart attack,
and kidney disease. Derivatives of oxadiazole have intriguing pharmacological
characteristics exhibiting strong anti-inflammatory and analgesic effects.
In another study, the compounds with strong anti-inflammatory and antitumor
action were synthesized. With ortho, meta, and para substituents in the phenyl ring,
a significant reduction in edema was observed, with respective edema inhibition
rates of 55%, 67%, and 67% was observed that were very close to those of aspirin
(68%) and ibuprofen (73%) (Bezerra et al. 2005). Compounds synthesized by
Omar and co-workers (Omar et al. 1996) exhibit strong anti-inflammatory effects
on histamine-induced abdominal edema in rats. These compounds had superior
anti-inflammatory effectiveness compared to ibuprofen. Based on a 200 mg/kg dose
of ibuprofen and mean time (minute standard error), anti-inflammatory actions were
considered. Ibuprofen’s mean time was 6.33 ± 0.96 min, while compounds 99–103’s
mean time ranged from 6.91 ± 0.88 to 14.56 ± 0.29 min. The 3-aryl 5-propyl 1, 2, 4
oxadiazole derivatives were synthesized (Srivastava et al. 2003) and evaluated for the
development of new NSAIDs that could specifically inhibit the COX2 enzyme, which
oversees producing prostaglandins and other mediators linked to the inflammatory
process. Using aspirin as a reference medication, the synthesized compounds were
tested for their anti-inflammatory efficacy. These substances demonstrated strong
anti-inflammatory efficacy, with edema inhibition ranging from 9.73% to 26.57%.
Bhandari and co-workers (2008) reported a series of S-substituted phenacyl-1,3,4-
oxadiazole-2-thiol derivatives, which demonstrated significant anti-inflammatory
activity with percent inhibition values ranging between 71.05% to 74.23% when
compared to the reference drug diclofenac (percent inhibition = 71.3%) additionally;
these substances had potent analgesic properties. Fenbufen-based 3[5 (substituted
aryl)1,3,4oxadiazol2yl]1(biphenyl4yl) propan1ones were claimed to have been
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Oxadiazole in Medicine and Drug Discovery 157
synthesized and tested for their analgesic and anti-inflammatory properties. These
substances demonstrated considerable anti-inflammatory efficacy, inhibiting edema
by more than 55% (Husain et al. 2009). Data on the in vitro inhibition of COX
enzymes revealed that substances were more selective for COX2 than COX1. The
selectivity indices with 4 methoxy and 3, 4 dimethoxy substitutions were 29.9 and
36.1 for COX2, respectively, and their IC
50
values were 1.5 and 1.8 M. In one study,
schiff bases of 1,3,4 oxadiazoles associated quinazolin-4-one with analgesic and
anti-inflammatory activities are the best candidate (Dewangan et al. 2017).
With 47.84% and 42.33% inhibition, compounds demonstrated more powerful
anti-inflammatory action. The development of 1,3,4 oxadiazole-modified
benzothiazole derivatives as promising anti-inflammatory and antioxidant
compounds is also well documented. Indomethacin served as the reference
medication for the in vivo para xylene-induced mice ear edema model, which was
used to assess the anti-inflammatory effect. At 100 mg/kg, the compound exhibited
strong anti-inflammatory action with 57.35% inhibition with IC
50
values from 0.01
to 0.05 mmol/L, showing strong antioxidant activity (Zheng et al. 2020). Ascorbic
acid and diclofenac sodium were used as reference medications for the evaluation
of a novel series of 2,5-disubstituted 1,3,4 oxadiazole derivatives for their in vitro
anti-inflammatory and antioxidant effects. A molecular docking analysis revealed that
certain substances might fit snugly inside the COX2 enzyme’s active site cavity. The
docking score of the compound was 8.063, and its glide energy was 33.293 kcal/mol
(Kashid et al. 2020). By using the Griess assay, 3,5-disubstituted-1,3,4-oxadiazole
derivatives has been developed as prospective iNOS inhibitors and anti-inflammatory
drugs, using indomethacin as the reference medication. In the carrageenan-induced
paw edema test, compounds significantly reduced the generation of nitric oxide with
FRQFHQWUDWLRQVRI DQG ȝ0DW D GRVH RI
100 M. Compounds were shown to be bound in the iNOS active site, according to
molecular docking research (Koksal et al. 2021).
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Humans can easily contract the spreadable retrovirus, which is a causative agent
of AIDS, when an infected person’s immune system gradually fails (Hijikata et al.
1998; Baptista et al. 2010). The HIV-1 and HIV-2 viruses are the two varieties out
of which HIV-1 spreads more quickly than HIV-2 (Gilbert et al. 2003). The primary
cause of HIV infections worldwide is HIV 1. Initial testing is carried out using
an enzyme-linked immunosorbent assay to identify HIV-1 antibodies (ELISA).
Specimens that tested negative for HIV in the initial ELISA are thought to be
HIV-negative. It was discovered that certain oxadiazole hybrids had anti-HIV efficacy.
Novel 4 aryl 1, 2, 5 oxadiazole-3 yl carbamate compounds having potential anti-HIV
action were synthesized (Takayama et al. 1996). The synthesis of 5-(1-adamantyl)-
1,3,4-thiadiazole-2-thiones and 5-(1-adamantyl)-3-substituted aminomethyl-1,3,4-
oxadiazoline-2-thiones from 5-(1-adamantyl)-1,3,4-thiadiazoline-2-thione has been
synthesized. These compounds inhibited HIV-1 replication in MT Against HIV-1 at
2 ȝ0, the compounds showed moderate anti-HIV activity with more than 10% viral
replication (El-Emam et al. 2004). The synthesis of quinolone-based oxadiazoles
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158 Oxadiazole in Material and Medicinal Chemistry
and screening for their anti-HIV efficacy were reported. Drugs like azidothymidine
were commonly utilized. The highest therapeutic indices (TI) values against the
HIV-1VB59 and HIV-1UG070 strains were demonstrated. Instead of ortho and meta
positions, electron-donating compounds like methyl and methoxy groups on the para
position of the phenyl ring improved activity (Shah et al. 2018). In order to create
anti-HIV-1 drugs, 1,3,4 oxadiazole-substituted 4-oxo[1,2a] pyrimidine conjugates
were synthesized. The anti-HIV activity of compounds was inhibited by 18%, 26%,
and 29%, respectively. Drugs like azidothymidine were commonly utilized. The
activity was boosted more by substitutions in the para position of the phenyl ring
than in the ortho or meta position (Hajimahdi et al. 2013).
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Overusing drugs has increased antimicrobial and antibiotic resistance against
different bacterial and fungal species (Aminov et al. 2017). Multidrug resistance
(MDR) has also contributed to a worrying situation globally (Brown and Wright
2016). Resistance to treatments has increased over the past few decades, necessitating
the creation of novel hybrids that exhibit a wide range of antimicrobial properties. In
keeping with this, oxadiazoles will be crucial in creating novel antimicrobial drugs.
A new series of thiazole clubbed 1,3,4-oxadiazole derivatives were synthesized,
and their in vitro antibacterial properties were tested. The antibacterial properties
of compounds ranged from excellent to good. The substances worked well against
S. aureus, having corresponding MICs of 500 and 12.5 ȝJ/ml. E. coli was susceptible
to compounds with corresponding MICs of 50 and 12.5 ȝJ/ml. Some compounds
had a 25 ȝJ/ml MIC and were effective against Candida albicans (Desai et al.
2013). A series of 3’-acetyl-2’-aryl-5[3’-(6-methylpyridinyl)] compounds like
2,3-dihydro [1,3,4] oxadiazole and 3’-acetyl[2,2’-aryl[3,6-methylpyridinyl]-5’-
oxadiazole were synthesized. Evaluation of the antibacterial effects of 2,3-dihydro
[1,3,4] oxadiazoles on S. aureus, E. coli, P. aeruginosa, Aspergillus flavus,
Chrysosporium keratinophilum, and Candida albicans was tested. At 1 and 0.5 mg/ml
concentrations, compounds exhibit the largest zones of inhibition of 9–13 and
10–13 mm, respectively, demonstrating outstanding antibacterial activity against
S. aureus, E. coli, and P. aeruginosa. The investigated bacterial strains were
effectively inhibited by compounds that showed potent antibacterial properties
(Shyma et al. 2013). Compared to the common medication fluconazole, compounds
showed superior antifungal efficacy against A. flavus and C. keratinophilum.
These chemicals inhibited the enzyme L-glutamine: D-fructose-6-phosphate
amidotransferase and successfully docked into the active pocket of GlcN6P
(D-fructose-6-phosphate amidotransferase). Compared to typical medications,
compounds exhibit lower binding energies toward the target, measuring 3.71, 4.89,
DQGN-PROUHVSHFWLYHO\.KDOLOXOODKHWDOV\QWKHVL]HGVXEVWLWXWHG
phenyl) 5 (2,3 dihydro 1,4 benzodioxane 2 yl) 1,3,4 oxadiazoles and tested them for
antibacterial activity (Khalilullah et al. 2016). The test compounds were evaluated
for antibacterial activity against strains of bacteria from S. aureus, E. coli, and
B. subtilis, as well as for antifungal activity against A. niger , A. flavus, and C. albicans.
Compounds against the tested strains showed significant biological activity. As
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Oxadiazole in Medicine and Drug Discovery 159
ketol-acid reductoisomerase (KARI) inhibitors, a new family of Mannich and bis
Mannich bases with five substituted 1,3,4-oxadiazoles had been synthesized. The
compounds demonstrated outstanding in vitro inhibitory effects against rice KARI
and good in vitro antifungal and herbicidal activity against Brassica campestris.
Compounds had strong KARI inhibitory actions, with respective Ki values of
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5 substituted (1,3,4-oxadiazol-2-yl) quinoline derivatives were synthesized
(Salahuddin et al. 2015). Since different Gram-positive strains of Bacillus cereus
were suppressed at relatively low concentrations of the produced compounds, their in
vitro antibacterial activity was examined. The derivatives were most effective against
Klebsiella pneumonia and against B. cereus as pure ciprofloxacin. Additionally, it
was discovered that their presence significantly reduced the pathogenicity of many
Gram-negative bacteria that were multidrug-resistant, such as Proteus vulgarisAP169,
V ibr o cholera 765, and E. coli 35B. The MIC of the highly active compounds against
the tested species was 12.5 ȝJ/ml. As possible antibacterial agents, heterocyclic
compounds, including pyrimidine and oxadiazole, were effective against S. aureus
and E. coli, with MIC values of 50 ȝJ/ml and 12.5 ȝJ/ml, respectively. With a MIC
value of 50 ȝJ/ml, compounds showed good efficacy against S. aureus. With MICs of
100, 50, and 100 ȝJ/ml, respectively, compounds demonstrated promising antifungal
efficacy against C. albicans, A. niger, and Aspergillus clavatus. The results of the
docking investigation showed that the compounds were successfully docked into the
active site of DNA gyrase (PDB ID: 1KZN) (Desai et al. 2022a). Novel quinoline-fused
oxadiazoles showed excellent antibacterial activity with a MIC value of
25–50 ȝJ/ml against E. coli. According to the docking investigation, the chemicals
were successfully docked into DNA gyrase’s active site (PDB ID: 1KZN) (Salahuddin
et al. 2015). As possible antibacterial drugs, quinazoline clubbed thiazole and
1,3,4-oxadiazole heterocycles found to be effective against E. coli and S. aureus
with MIC values of 100, 62.5, and 50 ȝJ/ml respectively. The substances were
successfully docked into the active site of DNA gyrase, according to a molecular
docking analysis (PDB ID: 1KZN) (Desai et al. 2021). As Staphylococcal biofilm
inhibitors, 1,2,4-oxadiazole indole analogs were synthesized, which prevented the
growth of S. aureus ATCC 25923 biofilm and was found to be the most effective.
Their respective BIC
50
values were 9.7, 0.7, and 2.2 ȝM (Parrino et al. 2021).
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According to the WHO, Cancer causes 10 million deaths worldwide, and the
top cause of death for both men and women is lung cancer (WHO Report 2020).
Chemotherapy can be used to treat cancer when it is first discovered. The success
of the treatment depends on receiving timely care, such as a surgical procedure
combined with medicines and radiotherapy (Arruebo et al. 2011; Roy and Saikia
2016). When a cell’s functioning is out of balance, the cell’s gene transcription
program results in cell death (Zhao et al. 2022; Siegel et al. 2022). As a result, the
body’s cells proliferate out of control and spread throughout the entire body. With
over a hundred different forms, cancer is a major cause of death in both industrialized
and developing nations (Miller et al. 2022).
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160 Oxadiazole in Material and Medicinal Chemistry
The present treatment strategies are helpful, but the link between MDR and the
toxicity of anticancer drugs has made it necessary to develop new chemotherapeutic
drugs. It has been noticed that several 1,3,4-oxadiazole-containing compounds will
be exploited as anticancer medicines in the future based on their pharmacological
action. The issues with toxicity and MDR may be solved through the creation of
new chemotherapeutic drugs. 1,3,4-oxadiazole compounds have been reported as
tubulin inhibitors and possible cytotoxic agents. With GI values of 71.56% (growth
percentage (GP—28.44%) and 72.68% (GP—27.32%)), the synthesized analogs
have the highest levels of cytotoxicity among them at 10 ȝ0. This is a higher
value in a single-dose assay than the common medications gefitinib and imatinib.
With percent GIs of 102.71%, 95.44%, 92.75%, 92.29%, 91.81%, 89.59%, and
89.20%, the compound was extremely active against MDA-MB-468 (breast cancer),
HL-60(TB) (leukemia), NCI-H460 (non-small cell lung cancer), LOXIMVI,
UACC-62 (melanoma), SR (leukemia), and M14 (melanoma) cell lines (Ahsan et al.
2018). With percent GIs of 136.36%, 133.09%, 132.40%, 170.76%, 156.66%, and
141.96%, the compound was found to be highly active against UO-31 (renal cancer),
OVCAR-4 (ovarian cancer), HOP-92 (non-small cell lung cancer), 786-O (renal
cancer), RXF 393 (renal cancer), and SNB-75 (CNS cancer). Out of 55 cancer cell
lines, the compound was shown to be effective against 22–35. In common cell lines,
compounds show greater cytotoxicity than the established medications gefitinib and
imatinib. With GI50 values ranging from 1.61 to > 100 ȝ0, the compound shows
considerable cytotoxicity against the cancer cell types under investigation. With
respect to the tested cell line SNB75, the compound had the highest GI50 value
(1.61 ȝ0). The TGI and LC50 values were respectively 3.36 and > 100 ȝ0. The
average cytotoxicity was determined to be 14.38 ȝ0 for all examined cancer cell
lines. Tubulin polymerization is inhibited in vitro with IC
50
values of 2.8 ± 0.3
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compounds covered the pharmacophoric characteristics. The oxadiazoles docked at
the active site of tubulin, hence tubulin inhibition accounts for the likely mode of
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tested for their potential to inhibit EGFR tyrosine kinase (49% and 50% at 10 ȝ0)
and have antiproliferative effects on human breast cancer cells (MCF-7) in the range
of 0.73–2.00 ȝ0. According to molecular docking tests, a compound formed a
hydrogen bond with Met793, which engage strongly with the back of ATP-binding
sites, including those for lapatinib, since they had benzyl and allyl substituents
$ERXဨ6HULHWDO2QWKHRWKHUKDQGZLWKWKHEHQ]\OJURXS DQDUHQHဨDUHQH
interaction with Arg841 was observed. A series of benzimidazole-linked oxadiazole
compounds were tested for anticancer efficacy. By having IC
50
values that were like
the common medication gefitinib (0.081 and 0.098 ȝ0, respectively), compounds
showed improved binding affinity to the EGFR. With IC
50
values of 5.0 and 2.55
ȝ0, the compounds were more cytotoxic than 5 fluorouracil against the MCF-
7 cancer cell line. The interaction between N1 and Asp831 was demonstrated by
molecular docking studies. Due to the same hydrogen bond between Asp831 and N1
of the benzimidazole in both molecules, their binding modes are comparable (Akhtar
et al. 2017). Several imidazopyrimidinyl-1,3,4 oxadiazole hybrids were produced
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Oxadiazole in Medicine and Drug Discovery 161
and tested against various cancer cell lines, which showed strong anticancer activity
with a mean GP of 33.54. At a single dose of 10 ȝ0, it has strong cytotoxic action
against most tumor cell lines, with a GI50 value of 1.30–5.46 ȝ0. Additional testing
at five different dose levels (0.01, 0.1, 1, 10, and 100 M) revealed GI50 values
between 1.30 and 5.64 ȝ0 against the examined cancer cell lines. At a single dose of
10 ȝ0, the compound had the strongest activity against HOP-62 (non-small cell lung
cancer), with a GP of 65.54% to 72.94% (Subba Rao et al. 2016).
Furthermore, a Topo II-mediated DNA relaxation experiment shows that
the same substance can decrease Topo II activity. As demonstrated by molecular
modeling and the docking score of 8.29, the Topoisomerase enzyme is bound to it.
In a series of novel 5pyridyl1,3,4oxadiazole derivatives, the anticancer and cytotoxic
activity was investigated (Khalil et al. 2015). The 2 (benzylsulphanyl)-5aryl-
1,3,4-oxadiazole derivatives had EGFR inhibitory action, and the cytotoxic effect
of 5(pyridyl)-1,3,4-oxadiazolethiol derivatives against the MCF-7 breast cancer
cell line was assessed. Docking studies were conducted in order to determine the
likelihood that the target compounds may eventually develop into lead compounds
as a result of additional biological research. With IC
50
values of 0.010 and 0.012 ȝ0
and binding energy scores of –10.32 and –10.25, respectively, the compounds were
more active than the reference medication. With respective IC
50
values of 0.036 and
0.037 ȝ0 and binding energy scores of –9.98 and –9.79, compounds 187 and 188 were
DFWLYH$ VHULHV RI ဨဨVXEVWLWXWHGဨဨR[DGLD]ROဨဨ\O TXLQROLQဨ+ဨRQHDQGဨ
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R[DGLD]ROဨဨ\O@íဨSဨWRO\OR[\ဨTXLQROLQH GHULYDWLYHV ZHUH V\QWKHVL]HG 6DODKXGGLQ
et al. 2014a). The National Cancer Institute examined these chemicals for anticancer
potential and assessed their performance on a panel of 60 cell lines (NCI). The
average GP against the cancer cell lines under investigation was determined to be
66.23% for the tested compounds; the GI50 values ranged from 1.41 to 15.8 ȝ0 in
the one-dose experiment and from 0.40 to 14.9 ȝ0 in the five-dose assay. Previously,
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>@ဨR[DGLD]ROဨဨ\OPHWK\O@í+ဨEHQ]LPLGD]ROHV ZHUH V\QWKHVL]HG ZKLFK
showed in vitro anticancer efficacy against 60 cancer cell lines with a mean GP of
72.85–74.09 against the cancer cell lines under study. The compounds were very
active with growth percent of 32.73 and 47.56 for MDA-MB-468 (breast cancer),
SK-MEL28 (melanoma), NCI-H522 (non-small cell lung cancer), and UO-31 (renal
cancer) (Salahuddin et al. 2014b). Several novel 2,5 disubstituted 1,3,4 oxadiazole
derivatives were synthesized, demonstrating a sizable amount of DNA photocleavage
activity. According to the current study, oxadiazole derivatives had greater potential
for DNA photocleavage than isonicotinoyl hydrazones, and some changes to the
basic structure could eventually lead to the development of some chemotherapeutic
drugs (Kumar et al. 2015). Furthermore, 1,3,4-oxadiazole compounds were tested
for their anticancer and cytotoxic properties which exhibited strong in vitro
anticancer properties and cytotoxic activity. The percentage viability IC
50
against
hepatocellular carcinoma HepG2 was 21.2 and 12.4 ȝJ/ml, respectively. Compound
derivatives showed moderate anticancer activity against breast cancer MCF7 with a
percentage inhibition range of 26–50 ȝJPO%RQGRFNHWDO1ဨEHQ]\Oဨဨဨ
https://t.me/med1917
162 Oxadiazole in Material and Medicinal Chemistry
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RI DSSURSULDWH EHQ]\ODPLQH S\UUROHဨဨFDUEDOGHK\GH 1ဨLVRF\DQLPLQR WULSKHQ\O
phosphorane and carboxylic acid were synthesized (Ramazani et al. 2014). Using
an MTT assay, the anticancer effects of compounds were evaluated against several
cancer cell lines. In comparison to the conventional medication doxorubicin, these
substances demonstrated equivalent or superior cytotoxic activity against the A549,
HT29, and HT1080 cells with IC
50
values of 27.5, 20, 25.7, 13.3, 18, 25.1, 17.3,
20, and 45.3 ȝ0, respectively. With IC
50
values of 13.9 and 4.3 ȝ0, the compound
demonstrated superior cytotoxic action against the MCF-7 cancer cell line compared
to doxorubicin, which was four times as strong as doxorubicin, a commonly used
drug (Desai et al. 2022a).
By using intercalation binding of 1-substituted phenyl 3-(2-oxo-1,3,4-oxadiazol-
5-yl)-carbolines, the anticancer efficacy and ctDNA were investigated. With a
GI50 in the range of 0.67–3.20 ȝ0 against five cancer cell lines—breast (MCF7),
resistant ovarian (NCIADR/RES), lung (NCIH460), ovarian (OVCAR03), and
colon (HT29) cancer cell lines—a compound with an N, N dimethylaminophenyl
group demonstrated the best efficacy with the measured mean of GI50 was 1.68 ȝ0
(Savariz et al. 2014). In another study, a new variety of 5H-dibenzo [b,e] azepine-
6,11-dione derivatives with 1,3,4-oxadiazole units as possible anticancer drugs
for human ovarian cancer cell lines (OVCAR-3) has been produced. Using the
MTT assay and rucaparib as a reference medication, the investigated compounds
were evaluated against the OVCAR-3 cell line. The most effective compounds
against OVCAR-3 were compound 205 and compound 206, with IC
50
values of
DQGȝ0UHVSHFWLYHO\7KHVWURQJHVWPROHFXOHZDVGRFNHG
into the PARP-1 active site (PDB ID: 4RV6). Rucaparib’s position score was slightly
higher than the GBVI/WSA binding free energy of 206 in the S field, which was
13.4189 kcal/mol (He et al. 2018). As possible anticancer medicines, 1,3,4-oxadiazole
fused tetrazole amide derivatives have been synthesized. Using the MTT assay and
the standard medication doxorubicin, the antitumor efficacy of the compounds
was evaluated using three distinct human cancer cell lines A549, MDA-MB-231,
and MCF7. Compared to doxorubicin, compounds have the highest potency. With
IC
50
values of 1.77, 2.45, and 1.22 ȝ0 for the A549, MDA-MB-231, and MCF-
7 cell lines, the compound exhibited strong anticancer activity. With IC
50
values
of 1.02, 1.34, and 0.31 M for the A549, MDA-MB-231, and MCF7 cell lines, the
compound exhibited strong anticancer activity. The compound showed promising
anticancer activity with IC
50
values of 1.11, 2.90, and 1.90 ȝ0 against the A549,
MDA-MB-231, and MCF7 cell lines (Kotla et al. 2020). Also, 2(N-heterocycle)
substituted 1,3,4 oxadiazoles were synthesized as possible anticancer drugs. Using
the MTT assay and standard medications doxorubicin and 5 fluorouracil, the
synthesized compounds were tested for their anticancer efficacy against the three
distinct human cancer cell lines MCF7, HT-29, and HepG2. With IC
50
values of
DQGȝ0DJDLQVWWKH0&)+7DQG+HS*
cell lines, the compound demonstrated substantial anticancer activity. The compound
had IC
50
values of 0.86 ± 0.47, 0.78 ± 0.19, and 0.26 ± 0.15 against the MCF-7,
https://t.me/med1917
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