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Nano-CuFe2O3-catalyzed green synthesis of novel quinazolinone–tetrazole hybrids as anti-cancer agents

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Abstract

A novel green protocol has been developed for the synthesis of quinazolinone–tetrazole conjugates (7a–g, 8a–g and 9a–g) using recyclable nano-CuFe2O3 catalyst in water. Initially, 2-mercapto-3-substituted phenethylquinazolin-4(3H)-one (5a–c) was prepared by using nano-CuFe2O3 catalyst in water. Then, compounds (5a–c) were reacted with 1-bromo-3-chloropropane under nano-CuFe2O3 catalyst in water solvent to give S-alkylated quinazolinone core intermediate (6a–c), which was subsequently reacted with 1-substituted-1H-tetrazole-5-thiol (2a-g) by employing the similar reaction conditions to afford the final target compounds. The regioselective formation of C–S bond was unambiguously confirmed by single-crystal X-ray diffraction. The anti-cancer activity of the derivatives on various cancer cell lines such as SIHA, MD-AMB-231 and HepG2 was evaluated. Remarkably, compounds, 7f, 8f, 9a, 9d and 9f, showed potent activity in MD-AMB-231 cancer cell line (IC50: 9.13–10.3 µM), while the same derivatives showed significant potent activity in SiHa and HepG2 cancer cell lines (IC50: 17.46–27.0 µM). Most significantly, compound 7o (IC50: 8.15 µM) showed potent activity, compared to the drug etoposide (IC50: 18.11 µM) against MD-AMB-231 cell line. Flow cytometry analysis revealed that compounds 7f, 8f, 9a, 9d and 9f arrested the cell growth in the G1 phase in MD-AMB-231 cell line.

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Acknowledgements

The authors are thankful to the Director, Indian Institute of Chemical Technology, Hyderabad, for the encouragement, KD and GK are thankful to CSIR, New Delhi, India, for the award of research fellowships and thank Dr. Jagadeesh Babu Nanubolu for X‐ray analysis, Laboratory of X‐ray Crystallography. We thank CSIR for financial support under the 12th Five Year plan projects “Affordable Cancer Therapeutics (ACT)” (CSC 0301) and “Small Molecules in Lead Exploration (SMiLE)” (CSC0111).

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  1. Medicinal Chemistry & Pharmacology Division, Discovery Laboratory, CSIR–Indian Institute of Chemical Technology, Hyderabad, India

    Dileep Kommula, Praveen Kumar Chintakunta & M. S. R. Murty

  2. Centre for Chemical Biology, CSIR–Indian Institute of Chemical Technology, Hyderabad, India

    Koteswararao Garikapati

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Kommula, D., Chintakunta, P.K., Garikapati, K. et al. Nano-CuFe2O3-catalyzed green synthesis of novel quinazolinone–tetrazole hybrids as anti-cancer agents. Mol Divers 27, 425–441 (2023). https://doi.org/10.1007/s11030-022-10432-6

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