Recent Developments on Synthesis Strategies, SAR Studies and Biological Activities of β-Carboline Derivatives – An Update

The β-carboline skeleton is prevalent in a vast collection of naturally present alkaloids. Most of these alkaloids and their derivatives have been found to show significant biological properties, which facilitate the development of new synthetic methodologies for the modification of β-carboline core in order to develop high potential drugs. In this review, we highlight the recent developments and studies related to the design and synthesis of β-carboline derivatives which have been reported over the period of 2016-2021. Furthermore, various derivatives of β-carboline with important biological activities which include anti-cancer, anti-tuberculosis, anti-leishmanial, anti-fungal, anti-proliferative, anti-malarial, anti-metastatic and anti-chollinergic activity are presented. Notably, anticancer activities are reported for the salicylic acid based β-carboline hybrids, marine alkaloid related bisindoles and triazole based β-carboline derivatives, bivalent β-carboline and podophyllotoxin linked β-carbolines. N-pthalimido derivatives of 1-substituted-2-carboxamido-β-carbolines showed distinct anti-tuberculosis activity while N-hydroxy cinnamide hybrids displayed a high anti-proliferative activity. Furthermore, anti-fungal activities were observed on aryl-1,2,3-triazole-β-carboline hybrids and 2,6-difluoro-N-((1-(2,3,4-trimethoxyphenyl)-9H-pyrido[3,4-b] indol-3-yl)carbamoyl)benzamide. N-benzyl 1-(4-methoxy) phenyl-9H-β-3-carboxamide, 1,3,5-triazine hybrids and piperazinyl-β-carboline-3-carboxamide possessed a very good anti-leishmanial activity. N9 bivalent β-carboline hybrids and quaternary 2-phenyl-9-methyl-β-carbolinium hybrids were found to be a good anti-chollinergic agents. An anti-breast cancer activity has also been reported in the case of β-carboline-(phenylsulfonyl)furoxan hybrids.