Tailoring bisindolyl methane derivatives for dual applications: Substituent-directed probing of cyanide ions and anti-tubercular activity

[Display omitted] •Design and synthesis of compound 1 (single nitro-substituent) and compound 2 (three nitro substituents).•Detection of cyanide in aqeous medium via hydrogen bonding in 1, whereas Michael addition reaction in 2.•Change in the mode of binding of a specific analyte, merely by changing the number of un-reactive substituents.•Furthermore, a library of BIM compounds with different number of nitro groups at different positions (total 12) were designed for evaluation of anti-tubercular activity.•Detailed computational and docking studies for the cyanide detection mechanism and prediction of anti-tubercular activity of the BIM compounds. A pair of bisindolyl methane (BIM) compounds (1 and 2) were designed and their colorimetric response towards cyanide (CN−) ions were investigated in detail. In aqueous medium, the compound with single nitro-substituent (1) showed blue-shifted absorption maxima upon addition of cyanide ion, resulting in change in solution color from pink to yellow. On the contrary, the compound with three nitro functional groups (2), exhibited hypochromic shift along with initial, blue-shifted absorption maxima (color changed from pink to yellow to colourless). The mechanistic investigation indicated that the former observation could be attributed by cyanide-mediated hydrogen bonding interaction (or deprotonation), while the latter might be caused due to the Michael addition reaction. Interestingly, at alkaline pH, chemodosimetric interaction was observed with both the probe molecules. However, the rate of interaction was much faster for compound 2 than that observed for 1. A change in the mode of binding of a specific analyte, merely by changing the number of un-reactive substituents, is not much known in the literature. However, it will be extremely beneficial for future engineering of more efficient sensory systems. Furthermore, a library of BIM compounds with various number of nitro groups at different positions (total twelve) were synthesized for evaluation of anti-tubercular activity. Fortunately, some of the compounds were found to be as equally effective as the commercially available anti-tuberculosis drug, ethambutol (MIC: 1.56 µg/mL), whereas the compound 2 displayed a better anti-tubercular response (MIC: 0.78 µg/mL). This observation was further rationalized by docking studies with M. tuberculosis DprE1 in complex with the non-covalent inhibitor QN118.