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Design, synthesis and molecular docking of novel structural hybrids of substituted isatin based pyrazoline and thiadiazoline as antitumor agents

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Abstract

Cancer, which is considered to be the world’s most serious illness cause 8.2 million deaths and this rate may double by 2030. We herein report a new series of 3-(2-(p-substituted)-2-((5-phenyl-1,3,4-thiadiazol-2-yl)imino)-2-(p-substituted)ethylidene)indolin-2-one (15–19) and 5-substituted-5′-substituted phenyl-2′,4′-dihydrospiro[indoline-3,3′-pyrazol]-2-one derivatives (20–24) as potent anticancer agents. These compounds were evaluated for in vitro antitumor activity against the National Cancer Institute panel of 60 cancer cell lines. Among all the synthesized compounds, two compounds 15 and 16 showed remarkable antitumor activity with GI50 (MG-MID) values of 0.65 & 0.72 µM, respectively against Non-small cell lung cancer. To gain insight for mode of binding with Epidermal Growth Factor Receptor kinase enzyme, these compounds were further subjected to docking studies.

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Acknowledgements

The authors would like to thank the National Cancer Institute (NCI), Bethesda, MD, USA for performing the antitumor testing of the synthesized compounds.

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Authors and Affiliations

  1. Department of Pharmacy, Anurag Group of Institutions, Venkatapur (V), Ghatkesar (M), Medchal District, Hyderabad, Telangana, 500 088, India

    Kiran Gangarapu

  2. Dr. Macs Bio-Pharma Pvt Ltd, JNTUH Kukatpally, Hyderabad-85, Telangana, India

    Kiran Gangarapu & Anvesh Jallapally

  3. Department of Pharmaceutics, SVS School of Pharmacy, Ramaram, Hanamkonda, Warangal, Telangana, 506 009, India

    Gouthami Thumma

  4. Department of Pharmaceutical Chemistry, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, 506 009, India

    Sarangapani Manda, Ravi Jarapula & Sriram Rekulapally

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  1. Kiran Gangarapu
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  2. Gouthami Thumma
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  3. Sarangapani Manda
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Correspondence to Kiran Gangarapu.

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Gangarapu, K., Thumma, G., Manda, S. et al. Design, synthesis and molecular docking of novel structural hybrids of substituted isatin based pyrazoline and thiadiazoline as antitumor agents. Med Chem Res 26, 819–829 (2017). https://doi.org/10.1007/s00044-017-1781-5

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