Synthesis and biological evaluation of Schizandrin derivatives as potential anti-cancer agents

Eur J Med Chem. 2018 Apr 10:149:182-192. doi: 10.1016/j.ejmech.2018.02.066.

Devi Amujuri ¹, Bandi Siva ¹, B Poornima ¹, Katukuri Sirisha ², A V S Sarma ², V Lakshma Nayak ³, Ashok K Tiwari ³, U Purushotham ⁴, K Suresh Babu ⁵

Affiliations

1 Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India.
2 Centre for NMR & Structural Chemistry, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad, 500607, India.
3 Division of Medicinal Chemistry and Biotechnology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India.
4 Department of Chemistry, KL University, Vaddeswaram, Guntur, 522502, India.
5 Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India. Electronic address: suresh@iict.res.in.

PMID: 29501940 DOI: 10.1016/j.ejmech.2018.02.066

Abstract

A new series of Schizandrin (1) derivatives were synthesized utilizing the C-9 position of the Schizandrin core and evaluated for their cytotoxic activities against HeLa (cervical Cancer), A549 (lung Cancer), MCF-7 (breast Cancer) and DU-145 (prostate Cancer) cell lines. Among the synthesized series, 4e, 4f, 4g and 5 showed potent activities against tested cell lines. More significantly, compound 5 exhibited most potent cytotoxic activity against DU-145 with an IC₅₀ value of 1.38 μM which is comparable to the standard agent, doxorubicin. Further, flow cytometry analysis indicated that 5 arrested cells in G2/M phase and consequently leading to Apoptosis. Molecular docking analysis showed that 5 occupied the colchicine binding pocket of tubulin. Overall, the present study demonstrates that 5, as a mitotic-agent.

Keywords

Cytotoxic activities; Docking; Flow cytometric analysis; Schizandrin; Synthesis.

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