Synthesis and evaluation of novel sulfonamide analogues of 6/7-aminoflavones as anticancer agents via topoisomerase II inhibition

Rohini N Shelke; Dattatraya N Pansare; Aniket P Sarkate; Ishudeep K Narula; Deepak K Lokwani; Shailee V Tiwari; Rajaram Azad; Shankar R Thopate

doi:10.1016/j.bmcl.2020.127246

Synthesis and evaluation of novel sulfonamide analogues of 6/7-aminoflavones as anticancer agents via topoisomerase II inhibition

Bioorg Med Chem Lett. 2020 Jul 15;30(14):127246. doi: 10.1016/j.bmcl.2020.127246. Epub 2020 May 5.

Authors

Rohini N Shelke¹, Dattatraya N Pansare², Aniket P Sarkate³, Ishudeep K Narula³, Deepak K Lokwani⁴, Shailee V Tiwari⁵, Rajaram Azad⁶, Shankar R Thopate⁷

Affiliations

¹ Department of Chemistry, Prof John Barnabas Post Graduate School of Biological Studies, Ahmednagar College, Ahmednagar, Ahmednagar 414001, India.
² Department of Chemistry, Deogiri College, Station Road, Aurangabad 431 005, MS, India.
³ Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431 004, MS, India.
⁴ Department of Pharmaceutical Chemistry, R C Patel Institute of Pharmaceutical Education & Research, Shirpur 425405, MS, India.
⁵ Department of Pharmaceutical Chemistry, Durgamata Institute of Pharmacy, Dharmapuri, Parbhani 431401, MS, India.
⁶ Department of Animal Biology, University of Hyderabad, Hyderabad, 500046, India.
⁷ Department of Chemistry, Prof John Barnabas Post Graduate School of Biological Studies, Ahmednagar College, Ahmednagar, Ahmednagar 414001, India. Electronic address: srthopate@gmail.com.

PMID: 32527548
DOI: 10.1016/j.bmcl.2020.127246

Abstract

A series of new sulfonamide analogues of 6/7-aminoflavones were synthesized by using molecular hybridization approach. These new sulfonamide analogues were screened for antiproliferative activity against human hepatocellular carcinoma (HepG-2), human lung cancer cell line (A-549), human colorectal adenocarcinoma (Caco-2) cancer cell lines. Compounds 5p, 5q, 5t, 5v, 5w and 5x exhibited good anticancer activity against selected cancer cell lines. These compounds were further evaluated to predict their ability to inhibit topoisomerase-II enzyme. Compound 5x has shown potent antiproliferative activity (IC₅₀ value 0.98 µM) as compared to standard drug Adriamycin (IC₅₀ = 0.94 µM) indicating that these compounds exhibits anticancer activity via inhibition of topoisomerase-II enzyme. Docking results also have supported above observations by indicating that compounds are held in the active pocket by combination of various hydrogen and hydrophobic interactions with Top II-DNA-etoposide enzyme.

Keywords: Aminoflavones; Anticancer activity; Docking; Sulfonamide; topoisomerase-II.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
DNA Topoisomerases, Type II / metabolism*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Flavonoids / chemical synthesis
Flavonoids / chemistry
Flavonoids / pharmacology*
Humans
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
Sulfonamides / chemical synthesis
Sulfonamides / chemistry
Sulfonamides / pharmacology*
Topoisomerase II Inhibitors / chemical synthesis
Topoisomerase II Inhibitors / chemistry
Topoisomerase II Inhibitors / pharmacology*

Substances

Antineoplastic Agents
Flavonoids
Sulfonamides
Topoisomerase II Inhibitors
aminoflavone
DNA Topoisomerases, Type II