ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Design, synthesis, in vitro, and in vivo anti-cancer evaluation of the novel spirobibenzopyrans on epithelial cancer model of Drosophila melanogaster

Prashant Rai, Jyotsna Singh, Rohit Kumar, Srikrishna Saripella, and Nageswara Rao Golakoti

Department of Chemistry, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, India

E-mail: skrishna@bhu.ac.in

Received: 23 February 2022  Accepted: 4 June 2022

Abstract:

Abstract

A total of eight novel spirobibenzopyrans were synthesized by Claisen-Schmidt condensation reaction and have been characterized by ¹H NMR, ¹³C NMR, FT-IR, UV-Vis spectroscopy, and High-Resolution Mass Spectrometry. The purity of these synthesized compounds was determined by HPLC. The in vitro anti-cancer screening of these synthesized spirobibenzopyrans was carried out at National Cancer Institute (NCI), USA, against 60 human cancer cell lines. In light of the NCI results, the potent spirobibenzopyrans identified were compounds 1, 2, 4, and 5. COMPARE analyses of the potent compounds show a strong to considerable correlation to the marketed anti-cancer drug vinblastine sulfate (microtubule formation inhibitor). Furthermore, compounds 2 and 4 were taken up for their in vivo anti-cancer evaluation in the epithelial cancer model of Drosophila melanogaster and their lethal doses in both wild-type and mutant organisms were determined to be 300 μM . The anti-cancer studies of the spirobibenzopyrans have been supported with the molecular docking studies performed against the target protein c-Jun N-terminal kinase (JNK). Compound 4 showed the highest docking score of −8.3 kcal/mol among the compounds we have reported here. In addition, drug-likeness studies of the synthesized novel spirobibenzopyrans were carried out to find their potential as drugs.

Graphical abstract

Keywords: Synthesis; Spirobibenzopyrans; Anti-cancer studies; COMPARE analyses; Drosophila melanogaster; Docking studies; Drug-likeness

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-022-02321-x

Chemical Papers 76 (10) 6401–6413 (2022)