Synthesis of novel spirobibenzopyrans as potent anticancer leads inducing apoptosis in HeLa cells

Swayamsiddha Kar; Gayathri Ramamoorthy; Kartik Mitra; Naveen Shivalingegowda; Mahesha; Sai Kiran Mavileti; Lokanath Neratur Krishnappagowda; Mukesh Doble; Nageswara Rao Golakoti

doi:10.1016/j.bmcl.2020.127199

Synthesis of novel spirobibenzopyrans as potent anticancer leads inducing apoptosis in HeLa cells

Bioorg Med Chem Lett. 2020 Jun 15;30(12):127199. doi: 10.1016/j.bmcl.2020.127199. Epub 2020 Apr 18.

Authors

Swayamsiddha Kar¹, Gayathri Ramamoorthy², Kartik Mitra², Naveen Shivalingegowda³, Mahesha⁴, Sai Kiran Mavileti¹, Lokanath Neratur Krishnappagowda⁴, Mukesh Doble⁵, Nageswara Rao Golakoti⁶

Affiliations

¹ Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Andhra Pradesh 515134, India.
² Bioengineering and Drug Design Lab, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology, Madras, Tamil Nadu 600036, India.
³ Department of Physics, Faculty of Engineering & Technology, Jain University, Bangalore 562 112, India.
⁴ Department of Studies in Physics, Manasagangotri, University of Mysore, Mysuru 570 006, India.
⁵ Bioengineering and Drug Design Lab, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology, Madras, Tamil Nadu 600036, India. Electronic address: mukeshd@iitm.ac.in.
⁶ Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Andhra Pradesh 515134, India. Electronic address: gnageswararao@sssihl.edu.in.

PMID: 32331934
DOI: 10.1016/j.bmcl.2020.127199

Abstract

Spirobibenzopyrans are an unexplored class of therapeutics. We report the anticancer activity of novel spirobibenzopyrans, synthesized by a one-pot reaction and extensively characterized. Structure of one of the spirobibenzopyran has been determined by the single crystal XRD technique. The in vitro anticancer activity of these derivatives across the NCI 60-cell line panel was evaluated and for the first time their mechanism of action against HeLa cells was probed via cell morphology analysis and cell cycle analysis. They were determined to be apoptosis inducers with cell cycle arrest in G₀/G₁ and S phase suggesting CDK-4 protein inhibition and the inhibition of DNA replication. The DNA inhibition was studied and confirmed using the alkaline comet assay for the compound CHX-4MO-SAL showing S phase inhibition. Further, conformity with the in silico Lipinski's score signify the potential of spirobibenzopyrans as anticancer leads.

Keywords: Alkaline comet assay; Anticancer activity; Apoptosis inducers; FACs studies; Spirobibenzopyrans.

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
Benzopyrans / chemical synthesis
Benzopyrans / chemistry
Benzopyrans / pharmacology*
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HeLa Cells
Humans
Molecular Structure
Spiro Compounds / chemical synthesis
Spiro Compounds / chemistry
Spiro Compounds / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Benzopyrans
Spiro Compounds