Synthesis and evaluation of anti-plasmodial and cytotoxic activities of epoxyazadiradione derivatives

Eur J Med Chem. 2017 Jul 7:134:242-257. doi: 10.1016/j.ejmech.2017.04.016.

P Ashok Yadav ¹, Ch Pavan Kumar ¹, Bandi Siva ¹, K Suresh Babu ², Aparna Devi Allanki ³, Puran Singh Sijwali ³, Nishant Jain ⁴, A Veerabhadra Rao ³

Affiliations

1 Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
2 Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. Electronic address: suresh@iict.res.in.
3 CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500 007, India.
4 Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.

PMID: 28419927 DOI: 10.1016/j.ejmech.2017.04.016

Abstract

Epoxyazadiradione (1), a major compound derived from Neem oil, showed modest anti-plasmodial activity against CQ-resistant and CQ-sensitive strains of the most virulent human malaria Parasite P. falciparum. A series of analogues were synthesized by modification of the key structural moieties of this high yield natural product. Out of the library of all compounds tested, compounds 3c and 3g have showed modest anti-plasmodial activity against CQ-sensitive (IC₅₀ 2.8 ± 0.29 μM and 1.5 ± 0.01 μM) and CQ-resistant strains (IC₅₀ 1.3 ± 1.08 μM and 1.2 ± 0.14), while compounds 3k, 3l and 3m showed modest activity against CQ-sensitive strain of P. falciparum with IC₅₀ values of 2.3 ± 0.4 μM, 2.9 ± 0.1 μM and 1.7 ± 0.06 μM, respectively. Additionally, cytotoxic properties of these derivatives against SIHA, PANC 1, MDA-MB-231, and IMR-3 Cancer cell lines were also studied and the results indicated that low cytotoxic potentials of all the derivatives which indicating the high selectivity index of the compounds.

Keywords

Anti-plasmodial activity; Azadiracta indica; Epoxyazadiradione; P. falciparum; SAR studies.

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