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Simultaneous ultrasound- and microwave-assisted one-pot ‘click’ synthesis of 3-formyl-indole clubbed 1,2,3-triazole derivatives and their biological evaluation

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Abstract

An environment friendly, high yielding, promising one-pot protocol for the click reaction of N-propargyl-3-formylindole 2(a–b), chloroacetic acid/ester 3(a–b) and sodium azide, leading to the formation of 3-formyl-indole clubbed 1,4-disubstituted-1,2,3-triazole derivatives 4(a–b), 5(a–b) and 6(a–f) aided by CuI catalyst accomplished under acceleration of simultaneous ultrasound and microwave irradiation in a very short reaction time has been described. Further, acid derivative 4(a–b) is subjected to acid–amine coupling reaction with secondary amine (p–t) in the presence of HATU to afford 6(p–t) and 7(p–t). The perspective of this protocol is to get rid of the hectic preparation and handling of organic azide which are generated in situ. Consequently, this protocol blossoms the click process by making it environment benign, user-friendly, safe and clean technique. All the synthesized compounds have been preliminarily screen for their in vitro antimicrobial activity against a panel of pathogenic strains. The majority of compounds possess noticeably inhibitory action against E. Coli, S. Typhi, P. Aeruginosa, C. tetani, S. aureus and B. subtillis. Among all compounds, 6p and 7q exhibit excellent inhibitory action against E.Coli and P. Aeruginosa strain, respectively, as compared to standard drug. One compound 5b shows remarkable potency against fungal strain. Molecular docking study was carried out to understand binding of compound with protein. In silico ADME prediction was carried out to check physicochemical properties of synthesized compound.

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Acknowledgements

This research was supported by the Department of Chemistry, Sardar Patel University. All the authors are grateful to UGC, New Delhi for UGC-CPEPA Phase-II program sponsored under award letter no. F. No. 1–14/2002-2016(NS/PE) dated April 28, 2016, as well as UGC-CAS, Phase-II sponsored under award letter no. F-540/5/CASII/2018 (SAP-I) dated July 25, 2018, for the assistance in general. We also thankful to Microcare Laboratory, Surat, for the biological screening of the compounds reported herein. One of the authors (Jaydeep A Mokariya) is grateful to the CSIR, New Delhi, for a CSIR-JRF.

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  1. Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar, 388120, Gujarat, India

    Jaydeep A. Mokariya, Anirudhdha G. Kalola, Pratibha Prasad & Manish P. Patel

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  1. Jaydeep A. Mokariya
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Mokariya, J.A., Kalola, A.G., Prasad, P. et al. Simultaneous ultrasound- and microwave-assisted one-pot ‘click’ synthesis of 3-formyl-indole clubbed 1,2,3-triazole derivatives and their biological evaluation. Mol Divers 26, 963–979 (2022). https://doi.org/10.1007/s11030-021-10212-8

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