Furan-2-carboxamide derivative, a novel microtubule stabilizing agent induces mitotic arrest and potentiates apoptosis in cancer cells

B Shwetha; M Srinivasa Sudhanva; G S Jagadeesha; N R Thimmegowda; Vivek K Hamse; B T Sridhar; K N Thimmaiah; C S Ananda Kumar; Rangappa Shobith; K S Rangappa

doi:10.1016/j.bioorg.2020.104586

Furan-2-carboxamide derivative, a novel microtubule stabilizing agent induces mitotic arrest and potentiates apoptosis in cancer cells

Bioorg Chem. 2021 Mar:108:104586. doi: 10.1016/j.bioorg.2020.104586. Epub 2021 Jan 8.

Authors

Affiliations

¹ Department of Nanotechnology, CPGS, Visvesvaraya Technological University, Muddenahalli, Karnataka 562101, India.
² Adichunchanagiri Institute for Molecular Medicine, AIMS, Adichunchanagiri University, BG Nagara 571448, Karnataka 02, India; Faculty of Natural Sciences, Adichunchanagiri University, BG Nagara 571448, Karnataka, India.
³ Department of Chemistry, Govt. S. K. S. J. Technological Institute (Affiliated to Visvesvaraya Technological University), K R Circle, Bangalore, Karnataka 560001, India.
⁴ Faculty of Natural Sciences, Adichunchanagiri University, BG Nagara 571448, Karnataka, India.
⁵ Department of Chemistry, Maharani's Science College for Women, Palace Road, Bangalore, Karnataka 560001, India.
⁶ Division of Natural Science Northwest Mississippi Community College, University of Mississippi Campus, Desoto Centre, Southaven, MS 38671, USA.
⁷ Department of Nanotechnology, CPGS, Visvesvaraya Technological University, Muddenahalli, Karnataka 562101, India; Centre for Material Science, University of Mysore, Mysore, Karnataka 570006, India. Electronic address: csanandakumar@vtu.ac.in.
⁸ Adichunchanagiri Institute for Molecular Medicine, AIMS, Adichunchanagiri University, BG Nagara 571448, Karnataka 02, India. Electronic address: aimm@acu.edu.in.
⁹ Institution of Excellence, University of Mysore, Manasagangotri, Mysore, Karnataka 570006, India.

PMID: 33607574
DOI: 10.1016/j.bioorg.2020.104586

Abstract

The vital role played by microtubules in the cell division process, marks them as a potential druggable target to decimate cancer. A novel furan-2-carboxamide based small molecule, is a selective microtubule stabilizing agent (MSA) with IC₅₀ ranging from 4 µM to 8 µM in different cancer cell lines. Inhibition of tubulin polymerization or stabilization of tubulin polymers abrogates chromosomal segregation during cell division, results in cell cycle arrest and leads to cell death due to the delayed repair mechanism. A novel furan-2-carboxamide based small molecule exhibited potent anti-proliferative and anti-metastatic property In-Vitro against the panel of cancer cells. Annexin V-FITC/PI, double staining reveals potent cytotoxic effect of SH09 against HeLa cells. FACS analysis displays induction of G2/M arrest and accumulation of subG1 population of cells upon treatment with SH09. Molecular docking study unveils SH09 binding affinity to the Taxol binding pocket of tubulin proteins and MM-GBSA also confirms strong binding energies of SH09 with tubulin proteins.

Keywords: Anticancer agents; Apoptosis; Furan-2-carboxamide; Microtubule stabilizing agents.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Furans / chemical synthesis
Furans / chemistry
Furans / pharmacology*
Humans
Microtubules / drug effects*
Mitosis / drug effects
Molecular Structure
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Furans