Ultrasound Assisted Synthesis of 2-Substituted Benzofurans via One-Pot and Sequential Method: Their In Vitro Evaluation

Abstract

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.

Pd/Cu-catalyzed access to novel 3-(benzofuran-2-ylmethyl) substituted (pyrazolo/benzo)triazinone derivatives: theirin silico/in vitroevaluation as inhibitors of chorismate mutase (CM)

“…37) and its subsequent applications in the preparation of potential bioactive compounds. [38][39][40][41] In further continuation of this efforts we decided to adopt a similar one-pot synthetic strategy in the current study for accessing the targeted 3-(benzofuran-2ylmethyl) substituted (pyrazolo/benzo)triazinone derivatives. We used a similar reaction conditions reported by us previously 20,37a with some suitable modications as the use of terminal alkyne 1 for the coupling with 2-iodophenols was not explored earlier.…”

“…37) and its subsequent applications in the preparation of potential bioactive compounds. 38–41 In further continuation of this efforts we decided to adopt a similar one-pot synthetic strategy in the current study for accessing the targeted 3-(benzofuran-2-ylmethyl) substituted (pyrazolo/benzo)triazinone derivatives. Thus, the Pd/Cu-catalyzed coupling of the required terminal alkyne ( 1 ) [ e.g.…”

Sonochemical Synthesis of 6‐Substituted Indolo[3′,2′:4,5]pyrrolo[2,3‐b]quinoxaline Derivatives as Potential Cytotoxic Agents

“…have been reported and SIRT1 inhibitors such as sirtinol, splitomicin, and cambinol have caused growth arrest, senescence, or apoptosis in tumor cells. [10,11] Due to our longstanding interest in the identification of new inhibitors [12][13][14][15][16][17] of SIRT1 we focused on polynuclear fused N-heteroarene derivatives. Indeed, based on the report on antitumor / anticancer potential of compounds containing polynuclear fused N-heteroarene framework [18,19] (A, Figure 1) we synthesized indolo [3',2':4,5] pyrrolo [2,3-b]quinoxaline derivatives represented by B (Figure 1) as potential and novel antiproliferative agents.…”