Bis(indolyl)methane Alkaloids: Isolation, Bioactivity, and Syntheses

Abstract

Bis(indolyl)methane (BIM) alkaloids are an important group of bioactive natural products predominantly found in marine organisms. Thus, compounds like arsindoline A and B, vibrindole A, arundine, and trisindoline are found in marine bacteria, while the related compound, streptindole is obtained from Streptococcus faecium IB 37, found in human feces. In recent years, these molecules, which display a wide range of biological properties (antibacterial, antiviral, anti-oxidant, neurotoxic activity etc.), have attracted the attention of several synthetic and natural product chemists. This review lists selected bis(indolyl)methane analogues reported from different natural sources to date, together with their biological properties and synthesis. 1 Introduction 2 Occurrence, Isolation, Structure Elucidation, and Biological Activity 3 Synthetic Approaches towards Bis(indolyl)methanes 4 Conclusions Key words bis(indolyl)methanes, natural products, isolation, synthesis, bioactive metabolites P. J. Praveen (left) was born in Kerala, India in 1988; he received his M.Sc. in chemistry in 2010 from the University of Kerala, India. He worked as a Junior Research Fellow at the CSIR-National Chemical Laboratory, Pune till 2013 and then moved to the CSIR-National Institute of Oceanography. Currently, he is studying for a Ph.D. in organic chemistry (working in the area of isolation and synthesis of bioactive marine natural products) under the guidance of Dr. P. S. Parameswaran. P. S. Parameswaran (middle) was born in 1955 in Ernakulam (Kochi), India and received an M.Sc. (applied chemistry) from Kerala University and Ph.D. (topic: chemistry of marine natural products) from Goa University in 1995. He began his career as a lecturer at St Alberts College, Ernakulam in 1979 and later moved to the CSIR-National Institute of Oceanography, Goa as a scientist. Presently, he heads the regional center of the CSIR-NIO in Ernakulam. His research interests include the purification and structure determination of bioactive marine metabolites and the synthesis of heterocyclic compounds using domino and green chemistry techniques. Mahesh S. Majik (right) was born in Goa, India in 1981; he received his M.Sc. in organic chemistry in 2003 from Goa University, India. He worked as a Junior Research Fellow at the CSIR-National Institute of Oceanography, Goa till 2005. He was awarded a Ph.D. degree in organic chemistry (worked in area of domino reactions for natural product synthesis and organocatalyses) under guidance of Prof. Santosh G. Tilve in 2010. Immediately afterward, he started his post-doctoral research in the area of 'the synthesis of modified nucleoside for drug discovery' with the research group of Prof. Lak Shin Jeong at Ewha Womans University, Seoul, South Korea (2010-2012). Then he joined the CSIR-NIO, Goa as a Scientist fellow (QHS) and worked in the field of medicinal chemistry of marine natural products (2012-2014). Since September 2014, he is working as an Assistant Professor at Goa University, Goa, India. His current research interests ...

Synthesis of arylpiperazine substituted bisindolylmethanes as possible pharmacologically active new compounds

“…A mixture of compound 2 (252.15 mg, 1 mmol), 1-(3-(trifluoromethyl)phenyl)piperazine (535.2 mg, 1 mmol), and anhydrous K2CO3 (276 mg, 2 mmol) in MEK (10 mL) was heated at 80 o C for 16 h. After completion of the reaction with TLC control, the solvent was evaporated and the residue was purified by column chromatography using ethyl acetate/n-hexane (1:1) as the eluent to give pure product 16 [15]. White solid (300 mg, 75% isolated yield).…”

“…The most common method for the synthesis of BIMs involves consecutive nucleophilic addition of two molecules of indole (nucleophile) to an aldehyde (electrophile) as a one-pot reaction in the presence of a number of catalysts like Brønsted, Lewis acids such as LiClO4, In(OTf)3, Dy(OTf)3, Sc(OTf)3, CAN, ZrOCl2, InCl3, heteropoly acids, ionic liquids, surfactants. [15][16][17] In our previous work, several UV-active bis(indolyl)methanes were prepared in the presence of 1,3dibromo-5,5-dimethylhydantoin (DBDMH) 18 and the UV-absorbing activity were investigated both in solution and polymer substrate. This study focuses on design and discovery of new bisindolylmethanes including arylpiperazine group.…”

Microwave-assisted synthesis of novel 1-{[(diindolyl)methyl]benzyl}-2-{[(diindolyl)methyl]phenyl}-1H-benzimidazole scaffold via two-consecutive multicomponent reaction

“…It is known that natural scaffolds containing either bis(indolyl)methane or benzimidazole core have been considered biologically relevant in the search of new potential applications as candidates with pharmaceutical activity. [1][2][3][4][5] Even though indole-3-carbinol 1 and their metabolic products such as 3,3´-diindolylmethane (DIM) 2 and the oligomers 3-4 have shown renewed anticancer properties; 6,7 another naturally occurring indole alkaloids featuring a central azaheterocyclic core decorated with either 1H-indol-3-yl or bis(1H-indol-3-yl)methane moieties have gained a prominent position as promising cytotoxic, antifungal and antibiotic agents with innovative mechanism of action.…”

Streptindole and Its Derivatives as Novel Antiviral and Anti-Phytopathogenic Fungus Agents

“…23 Studies revealed that streptindole exhibited DNA-damaging and genotoxic properties. 24 We have been committed to the development of new antiviral candidates based on indole natural products for a long time. Streptindole with a simple structure has aroused our great interest.…”