Background: Compounds containing furo[3,2-b]pyridine framework have shown interesting pharmacological properties including anticancer activities. Though these compounds are generally synthesized via the heteroannulation processes involving acetylenic derivatives some of them are not straightforward. Objective: To explore a series of 2-substituted furo[3,2-b]pyridines for their cytotoxic properties against cancer cell lines in vitro. Methods: We have developed a convenient synthesis of 2-substituted furo[3,2-b]pyridines via sequential (i) C-C coupling followed by (ii) C-O bond forming reactions in a single pot. The reactions were performed under ultrasound irradiation in the presence of Pd/C as an inexpensive, stable and widely used catalyst. A range of 2-substituted furo[3,2-b]pyridines were synthesized via coupling of 3-chloro-2-hydroxy pyridine with terminal alkynes in the presence of 10% Pd/C-CuI-PPh3-Et3N in EtOH. The in vitro evaluation of all these compounds was carried out against MDAMB-231 and MCF-7 cell lines and subsequently against SIRT1. Results: The furo[3,2-b]pyridine derivative 3b showed encouraging growth inhibition of both MDAMB-231 and MCF-7 cell lines and inhibition of SIRT1. The compound 3b also showed apoptosis inducing potential when tested against MCF-7 cells. Conclusion: The Pd/C-Cu catalysis under ultrasound accomplished a one-pot and direct access to 2-substituted furo[3,2-b]pyridine derivatives some of which showed anticancer properties.

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In the current study, we have explored 6‐substituted indolo[3′,2′:4,5]pyrrolo[2,3‐b]quinoxaline derivatives as potential cytotoxic agents. These compounds were readily prepared via the reaction of 2‐chloro‐3‐(2‐chloro‐1H‐indol‐3‐yl)quinoxaline with an appropriate amine under ultrasound irradiation in good to acceptable yields. The in vitro testing of all these compounds against MDA‐MB‐231 and MCF‐7 cell lines using a cell‐based assay and then against SIRT1 (or sirtuin 1) using an enzyme‐based assay was performed. The compound 3 a [i. e. 6‐(4‐methoxybenzyl)‐6,7‐dihydroindolo[3′,2′:4,5]pyrrolo[2,3‐b]quinoxaline] showed promising growth inhibition of both MDA‐MB‐231 and MCF‐7 cell lines (61 and 54 % at 10 μM, respectively) and inhibition of SIRT1 (IC50∼2.09±0.40 μM in vitro). Moreover, molecular modelling studies indicated interaction of 3 a with several residues e. g. GLU345, ILE347, PHE273, ILE270, PHE312, PRO271, ILE279, ILE316 at the active site of SIRT1 with estimated total energy=−99.90 kcal/mol and the ADME prediction in silico suggested 3 a as a potential hit molecule.