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.

Background: The 2-substituted benzofuran framework has attracted enormous attention due to its presence in a range of bioactive compounds and natural products. While various methods for the synthesis of 2- substituted benzofuran derivatives are known, several of them suffer from certain drawbacks. Objective: The main objective of this work was to explore a series of 2-(het)aryl substituted benzofurans derivatives for their cytotoxic properties against cancer cell lines in vitro. Methods: In our efforts, we have developed a one-pot synthesis of this class of compounds via sequential C-C coupling followed by C-Si bond cleavage and subsequent tandem C-C/C-O bond-forming reaction under ultrasound irradiation. The methodology involved coupling of (trimethylsilyl)acetylene with iodoarenes in the presence of 10% Pd/C-CuI-PPh3-Et3N in MeOH followed by treating the reaction mixture with K2CO3 in aqueous MeOH and finally coupling with 2-iodophenol. A variety of 2-substituted benzofurans were synthesized using this methodology in good yield. All the synthesized compounds were tested in vitro against two cancer cell lines, e.g. MDAMB-231 and MCF-7 cell lines subsequently against SIRT1. Results: The benzofuran derivative 3m showed encouraging growth inhibition of both MDAMB-231 and MCF- 7 cell lines and significant inhibition of SIRT1. The compound 3m also showed a concentration-dependent increase in the acetylation of p53. Conclusion: Our efforts not only accomplished a one-pot and direct access to 2-(het)aryl substituted benzofurans but also revealed that the benzofuran framework presented here could be a potential template for the identification of potent inhibitors of SIRT1.

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.

In view of remarkable biological properties including anticancer activities of N-aryl pyrazoles we have explored N-(2-methoxyphenyl) substituted pyrazoles and related derivatives as potential cytotoxic agents. In silico methods were adopted to understand/predict the biochemical and physiological effects, toxicity, and biological profiles of these compounds thereby assessing the potential drug-likeness of the hit molecule. The target compounds were conveniently prepared via a sonochemical method involving the CÀ N bond forming reactions in the presence of CuI in DMSO. A library of N-aryl pyrazole derivatives were synthesized via coupling of iodoarenes with pyrazole whereas the use of other N-heteroarene such as imidazole and pyrrole in place of pyrazole afforded the corresponding product. The in vitro evaluation of all these compounds was carried out against MDAMB-231 and MCF-7 cell lines and subsequently against SIRT1. The pyrazole derivative 3 c showed encouraging growth inhibition of both MDAMB-231 and MCF-7 cell lines (59 and 48 % at 10 μM, respectively) and inhibition of SIRT1 (IC 50 ∼ 6.21 � 0.42 μM) in vitro. The molecular docking studies suggested H-bonding (involving OMe group), Van der Waals and hydrophobic interactions of 3 c with important amino acid residues in the catalytic domain of SIRT1. Overall, cell-based as well as enzyme assay, molecular modelling, in silico ADME/TOX prediction and in vitro stability studies suggested 3 c as a potential hit molecule.