C-30 analogues of betulinic acid as potent cytotoxic agents: design, synthesis, biological evaluation and in-silico studies

Abstract

In an endeavour to improve the anti-cancer activity of betulinic acid (BA), a series of C-30 derivatives were envisaged and synthesized with a novel synthetic approach. All the derivatives were evaluated for cytotoxic activity by MTT assay against six different human cancer cell lines: prostate (PC3), lung (A549), human hepatocellular carcinoma (HepG2), human leukemia (Molt-4), pancreatic (Panc-1) and breast (MCF-7). The data revealed that compound 16 was observed most promising cytotoxic agent with IC₅₀ values of 7.43 μM, 9.1 μM, and 9.64 μM against A549, MCF-7, and PC3 cancer cell lines respectively. A further mechanistic study confirmed compound 16 showed significant cell death by arresting the cell cycle in the G1 phase and inducing apoptosis in A549 cells.

Communicated by Ramaswamy H. Sarma

Keywords:

• Betulinic acid
• cancer
• cytotoxicity
• G1 phase
• apoptosis
• in silico studies

Acknowledgements

The first author wish to thank ICMR, New Delhi for their generous funding for the award of senior research fellowship. The authors are also thankful to the staff of instrumentation division of CSIR-IIIM, Jammu for recording the spectroscopic (NMR and HRMS) data. The first author wishes to thank the Directors of CSIR-IIIM, Jammu and CSIR-IMMT, Bhubaneswar for providing the lab facility and support for this work. The manuscript is dedicated to my supervisor Late Dr. P.L. Sangwan for his support and guidance during the time of my doctoral work.

Supporting information

The ¹H NMR, ¹³C NMR, DEPT135, and HRMS spectral data were provided in the supporting information section.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.