Synthesis of arylpiperazine substituted bisindolylmethanes as possible pharmacologically active compounds

Bisindolyl methanes (BIMs) are a group of alkaloids which has a basic skeleton of two indole groups bridged by single carbon at 3 and 3' position. Several Indole derivatives are known to display promising biological properties such as antibacterial, neurotoxic, antioxidant, antiviral, etc. A few of these compounds are used as pesticides while some serve as new drug leads for treatment of depression and anxiety. Even the structurally prosaic bis(3-indolyl)methane (BIM), a metabolite of naturally occurring indole-3-carbinol, was effective in cancer chemotherapy. It induces unique responses such as growth inhibition, apoptosis, and antiangiogenic activities in various cancer cell lines and tumors. 1,1-Bis(3-indolyl)-1-(p-bromophenyl)methane, in its turn, inhibits colon cancer cell and tumor growth. The common route for the synthesis of bis(indolyl)methanes is electrophilic substitution reaction of indoles with the aromatic or aliphatic aldehyde and ketones catalyzed by protic acids or Lewis acids. However, Lewis acids are required in excess because it is destroyed by the presence of even small amount of moisture or when trapped by nitrogen present in heterocycles. In recent years, synthesis of this class of molecules under mild conditions have been reported with promoters such as SnCl2.2H2O, TCBDA, PCBS, Silica-H2SO4, P2O5/SiO2, SbCl3, Alum etc. Piperazine is a heterocyclic compound containing four carbon atoms and two nitrogen at 1 and 4 position (as called 1,4-hexahydropyrazine). Piperazines are a broad class of chemical compounds with many important pharmacological properties. Nitrogen in piperazine ring plays an important role in biological research and drug manufacturing industry including the proportion of anthelmintic, antiallergic, antibacterial, antihistaminic, antiemetic and antimigrainic agent. In recent years, many organocatalytic/metal free synthetic pathways towards bisindolylmethanes have been reported. In the present work, we combined bisindolylmethanes with arylpiperazines using hydrophobic moiety (alkyl chain) to obtain new heterocyclic molecules (compounds 2-12) that can be evaluated in pharmacologically and may be more active than the already active bisindolylmethane alkaloids. Keywords: Bisindolylmethanes, Arylpiperazines, Biologically active compounds.