Synthesis of novel multifunctional spirobibenzopyran derivatives: Crystal structure, In-silico study, anticancer activity and antimycobacterial activity

Abstract

A Novel series of multifunctional Spirobibenzopyran derivatives were synthesized from derivatives of 2-hydroxybenzaldehyde and various ketones with α-hydrogen. Single crystal X-ray analysis was obtained for three compounds. The drug-likeliness and toxicity predictions confirmed minimal toxicity (class IV). Docking showed good complementarity of active compounds with the colchicine binding site of tubulin. Molecular docking showed that methoxy group containing compound-7 binds to the proposed target (colchicine active site) with highest docking score. The synthesized molecules were evaluated as potent anticancer agents against MCF-7, MDA-MB-231 (human breast carcinoma) and A549 (human lung carcinoma) cell lines using MTT assay. In general, substituted spirobibenzopyran compounds showed higher activity towards the lung cancer cell line (A549) and breast cancer cell line (MCF-7 and MDA-MB-231) as compared to unsubstituted spirobibenzopyran molecule. They exhibit competitive results with the reference drug Crizotinib and 5-Fluorouracil. Spirobibenzopyran compound-5 with two phenolic hydroxyl group revealed a promising drug profile, inhibiting cell growth and proliferation against lung cancer cell line (A549) with IC50 value 13.54 ± 3.46 µM. Methoxy substituted compound-7 showed best potency among all spirobibenzopyrans against triple negative cell line MDA-MB-231 having IC50 value 18.96 ± 5.77 µM. As per our best knowledge this is the first report of Antimycobacterial activity of spirobibenzopyrans against Mycobacterium smegmatis MC2 155. Compound-6 with polar carboxylic acid functionality showed enhanced Antimycobacterial activity (MIC 5 µg/mL) as compared to standard drug Rifampicin.