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Synthesis and evaluation of a novel series of 6-bromo-1-cyclopentyl-1H-indazole-4-carboxylic acid-substituted amide derivatives as anticancer, antiangiogenic, and antioxidant agents

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Abstract

A series of novel indazole derivatives has been synthesized and evaluated for anticancer, antiangiogenic, and antioxidant activities. The capability of the synthesized compounds 11a–x to hinder the viability of three human cancer cells lines, HEP3BPN 11 (liver), MDA 453 (breast), and HL 60 (leukemia), were assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. Among the compounds 11a–x screened, 11c and 11d showed the higher inhibitory activity on the viability of HEP3BPN 11 (liver), when compared with the standard methotrexate. These compounds were further tested to evaluate their potential to inhibit the proangiogenic cytokines associated with tumor development. Compound 11c was found to be a potent antiangiogenic agent against TNFα, VEGF, and EGF, whereas 11d showed potent antiangiogenic activity against TNFα, VEGF, IGF1, TGFb, and leptin inhibition. All the compounds 11a–x were screened for their antioxidant activities using 2,2-diphenyl-1-picryl hydrazine (DPPH), hydroxyl (OH), and superoxide radical (SOR) scavenging activity. Compounds 11n, 11p, 11q, and 11v have shown significant OH radical scavenging activities, also compounds 11c, 11h, and 11k were found to have a DPPH radical scavenging activity and compounds 11a and 11m exhibited better SOR scavenging activity when compared with the reference compound ascorbic acid. In silico molecular docking analysis revealed important structural insights behind observed anti TNFα effect by present indazole compounds.

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Acknowledgements

RNG thanks the financial assistance through DRDP, DST-PURSE schemes of SPPU Pune. SSK is sincerely thankful to UGC, New Delhi, India, for providing Maulana Azad National Fellowship (SRF).

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Author notes

  1. These authors contributed equally: Ajay S. Sawant, Sonali S. Kamble

Authors and Affiliations

  1. School of Chemical Sciences, Swami Ramanand Teerth Marathwada University, Nanded, 431 606, Maharashtra, India

    Ajay S. Sawant, Parshuram M. Pisal & Sanjay S. Sawant

  2. School of Life Sciences, Swami Ramanand Teerth Marathwada University, Nanded, 431 606, Maharashtra, India

    Sonali S. Kamble

  3. Bioinformatics Centre, Savitribai Phule Pune University, Pune, Maharashtra, 411007, India

    Rohan J. Meshram

  4. Department of Microbiology, Adarsha Mahavidyalaya, Amaravati, Maharashtra, India

    Vilas A. Kamble

  5. Organic Chemistry Research Laboratory, Department of Chemistry, Institute of Science, Nagpur, Maharashtra, India

    Vinod T. Kamble

  6. Department of Biotechnology, Savitribai Phule Pune University, Pune, 411007, Maharashtra, India

    Rajesh N. Gacche

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  1. Ajay S. Sawant
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Sawant, A.S., Kamble, S.S., Pisal, P.M. et al. Synthesis and evaluation of a novel series of 6-bromo-1-cyclopentyl-1H-indazole-4-carboxylic acid-substituted amide derivatives as anticancer, antiangiogenic, and antioxidant agents. Med Chem Res 29, 17–32 (2020). https://doi.org/10.1007/s00044-019-02454-x

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