Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5596_Библиотеки_им_академика_М_И_Перельмана

Carbolines are a diverse class of nitrogen- containing cyclic alkaloids, and good places to look for them include insects, plants, microorganisms, marine organisms, mammalian tissues, and physiological uids (Cao et al. 2007). Carbolines are a type of secondary heterocyclic amine that typically consist of an indole ring that has been fused to a pyridine ring. It has been hypothesized that the amino acids tryptamine and tryptophan are involved in the production of beta- carboline in some capacity (Maresh et al. 2008). Nearly 140 distinct β- carboline with a wide range of structures have been discovered in nature thus far. Traditional medicines in many countries make use of the β- carboline harman, while P. harmala species are rich in the more potent β- carboline norharman (Moloudizargari et al. 2013; Stoic 1999). Inhibition of microbial growth on antibiotic- resistant strains has been linked to the presence of multiple carbolines,

which paves the way for the development of new antimicrobials based on carboline (Shin et al. 2010). The cyanobacterium N. harveyana also produce β- carboline norharmane in quantitative amount (Volk 2005). Nostocarboline was isolated from Nostoc species (Becher et al. 2005). An ascidian, Didemnum sp., was used to isolate a rare N- N- coupled β- carboline dimer (Kearns and Rideout 2008; Koehn and Carter 2005; Mishra and Tiwari 2011; Chen et al. 2022).

Marine tunicates of the genus Eudistoma have been the subject of extensive chem­ical and biological study. Many β- carboline containing alkaloids have been isolated from various Eudistoma species since Wang and his colleagues rst reported their structures (Figure 2.2). Biosynthesis of these β- carbolines is thought to involve the coupling of tryptophan with a second amino acid, as demonstrated by in vivo anti­microbial studies with E. olivaceum. New natural metabolites with a β- carboline base have been isolated from the tunicate Eudistoma. These metabolites have been given the names Eudistomins Y 1- 7. These new metabolites were previously isolated from marine metabolites, and the benzoyl group is attached to the β- carboline nucleus at the C- 1 position. Eudistomins Y 1- 7 have the potential to inhibit the growth of bac­teria; however, only Eudistomin Y 6 displays a trace amount of antimicrobial activity against Gram- positive microbes S. epidermis and B. subtilis at concentrations of 100 μM without causing cytotoxicity (Wang et al. 2008).

Carboline derivatives with a benzylidine at position 1 were studied for in vitro cytotoxicity on a variety of human cell lines. The most intriguing cytotoxic activities were those of N2- benzylated β- carbolinium bromates. Both compounds were found to be the most effective against 10 different human tumour cell lines, with IC50 values

Depending on the saturation level and the location of the N atom in the C ring, carbolines are categorized as α- , β- , γ- , or δ- carbolines from a more global structural perspective (Smirnova et al. 2011; Singh and Batra 2012). There is a broad spectrum of biological behaviours among members of this family (Piechowska et al. 2019; Dai et al. 2018; Cao et al. 2007). The fascinating structural diversity and therapeutic potential of β- carboline- containing natural products and their synthetic derivatives has attracted the attention of a number of researchers (Maity et al. 2019; Domínguez and Pérez- Castells 2011). Numerous pharmaceuticals, including vinpocetine, cipargamin, vinamine, brovincamine, yohimbine, tadalal, abecarnil, reserpine, and lurbinectedin 30– 38, contain this one- of- a- kind chemical (Figure 2.8). The leaves of the plant Vinca minor (lesser periwinkle) contain the indole alkaloid vincamine, a monoterpenoid carbazole alkaloid that makes up 25– 65% of the plant’s total indole alkaloids. In Europe, vincamine is prescribed for the treatment of vascular and degenerative dementias. Vinpocetine is a vincamine derivative that has been synthesized for use in medicine and nutrition. Antiaddictive and antidiabetic properties of vincamine derivatives are another area of investigation. Common dosage forms include extended- release tablets. Potentially nootropic, it has also been investigated as a possible anticancer drug. The vinca alkaloid vincamine is the starting point for the synthetic compound vinpocetine, also known as ethyl apovincaminate. Vinpocetine has been used for more than 30 years to treat cerebrovascular disorders like stroke and dementia in many Asian and European countries. There are numerous nootropic dietary supplements on the market that contain vinpocetine.