Design and synthesis of novel conformationally constrained 7,12-dihydrodibenzo[b,h][1,6] naphthyridine and 7H-Chromeno[3,2-c] quinoline derivatives as topoisomerase I inhibitors: In vitro screening, molecular docking and ADME predictions.

Autor: Kardile RA; Department of Chemistry, Ahmednagar College, Ahmednagar 414001, Maharashtra, India., Sarkate AP; Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, Maharashtra, India., Borude AS; Department of Chemistry, Ahmednagar College, Ahmednagar 414001, Maharashtra, India., Mane RS; Department of Chemistry, Dr. S. D. D. Arts College and Commerce and Science College, Wada 421303, Maharashtra, India., Lokwani DK; Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education & Research, Shirpur 425405, Maharashtra, India., Tiwari SV; Department of Pharmaceutical Chemistry, Durgamata Institute of Pharmacy, Dharmapuri, Parbhani 431401, Maharashtra, India., Azad R; Department of Animal Biology, University of Hyderabad, Hyderabad 500046, India., Burra PVLS; Department of Biotechnology, KLEF University, Vaddeswaram 522502, Andhra Pradesh, India., Thopate SR; Department of Chemistry, S. S. G. M. College, Kopargaon 423601, Maharashtra, India. Electronic address: srthopate@gmail.com.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2021 Oct; Vol. 115, pp. 105174. Date of Electronic Publication: 2021 Jul 16.
DOI: 10.1016/j.bioorg.2021.105174
Abstrakt: Novel non-camptothecin (non-CPT) class of conformationally constrained, hitherto unknown 7,12-dihydrodibenzo[b,h][1,6] naphthyridine and 7H-Chromeno[3,2-c] quinoline derivatives have been designed, synthesized and evaluated for anti-cancer activity. In vitro anti-proliferation evaluation against human cancer cell lines (A549 and MCF-7) exhibited significant cytotoxicity. Among the derivatives (8-24), 8 (IC 50 0.44 μM and IC 50 0.62 μM) and 12 (IC 50 0.69 μM and IC 50 0.54 μM) were identified as the most promising candidate against A-549 and MCF-7 cancer cell lines respectively. Topo I inhibitory activity of 8 and 12 suggested that, they may be developed as potential anti-cancer molecules in future and rationalized by docking analysis with effective binding modes. Further, in silico ADME prediction studies of all derivatives were found promising, signifying the drug like properties. In precise, the present investigation displays a new strategy to synthesize and emphasis on anticancer activities of conformationally constrained dibenzo[b,h][1,6] naphthyridine derivatives and Chromeno[3,2-c] quinoline derivatives in the context of cancer drug development and refinement.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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