Review of ß-carboline and its derivatives as selective MAO-A inhibitors.

As flavin adenine dinucleotide (FAD)-dependent enzymes, monoamine oxidases (MAOs) catalyze the oxidative deamination of various endogenous and exogenous amines. MAO-A inhibitors are thought to be effective therapeutic agents for treating neurological diseases including depression and anxiety. Due to the academic challenge of developing new human (h) MAO-A inhibitors and the potential for discovering substances with remarkable properties compared to existing MAO-A inhibitors, numerous research groups are looking into novel classes of chemical compounds that may function as selective hMAO-A inhibitors. ß-Carbolines are reported to be a prominent class of bioactive molecules exhibiting MAO-A inhibition. Chemically, ß-carboline is a tricyclic pyrido-3,4-indole ring. It has only recently been discovered that this chemotype has highly effective and specific MAO-A inhibitory activity. In this review, structure-activity relationship studies included in particular research publications from the 1960s to the present are discussed with regard to ß-carboline and its analogs. This comprehensive information helps to design and develop a new family of MAO-A inhibitors for the management of depressive disorders.

A Review on Benzimidazole Scaffolds as Inhibitors of Mycobacterium tuberculosis Mycolyl-arabinogalactan-peptidoglycan Complex Biosynthesis.

BACKGROUND: Tuberculosis is one of the oldest known infectious diseases to mankind, caused by Mycobacterium tuberculosis. Although current treatment using first-line anti-tubercular drugs is proven to be effective, an infection caused by resistant strains, as in multidrug-resistant and extensive drug- resistant tuberculosis is still an impending challenge to treat. OBJECTIVE: Our objective is to focus on reporting benzimidazole derivatives that are targeting mycobacterial membrane biosynthesis, particularly the mycobacterial mycolyl-arabinogalactanpeptidoglycan complexes. From the literature survey, it has been noted that targeting Mycobacterium tuberculosis cell membrane biosynthesis is an effective approach to fight against drug resistance in tuberculosis. METHODS: Articles on benzimidazole derivatives as inhibitors of proteins responsible for the biosynthesis of the mycobacterial mycolyl-arabinogalactan-peptidoglycan complex have been selected. RESULTS: By reviewing the anti-tubercular activity of the reported benzimidazole derivatives, we have concluded that a correlation between benzimidazole derivatives and their biological activity is found. It has been noted that benzimidazole derivatives with substitution at N1, C2, C5, and C6 positions have shown a greater affinity towards target proteins. CONCLUSION: Even though scientific advancement toward the prevention of tuberculosis has been quite significant in the past few decades, infection caused by resistant strains is a major concern. We have collected data on benzimidazole derivatives that inhibit the biosynthesis of mycolic acid, arabinogalactan and, peptidoglycan. From our observations, we conclude that majority of the molecules have given anti-tubercular activity in nanomolar range. Still there are few mycobacterial membrane biosynthesis proteins where benzimidazole as an inhibitor has yet to be explored.

Revealing the role of the benzyloxy pharmacophore in the design of a new class of monoamine oxidase-B inhibitors.

The conceptual layout of monoamine oxidase (MAO) inhibitors has been modified to explore their potential biological application in the case of neurological disorders for the time being. The current review article is an effort to display the summation of innovative conceptual prospects of MAO inhibitors and their intriguing chemistry and bioactivity. Based on this scenario, we emphasize the pivotal role of the benzyloxy moiety attached to scaffolds like oxadiazolones, indolalkylamines, safinamide, caffeine, benzofurans, α-tetralones, ß-nitrostyrene, benzoquinones, coumarins, indoles, chromones, and chromanone analogs, while acting as an MAO inhibitor.