Synthesis of novel ring-A fused hybrids of oleanolic acid with capabilities to arrest cell cycle and induce apoptosis in breast cancer cells.
Six novel oleanolic acid ring-A fused hybrids (5-10) have been synthesized by employing a four step protocol with the introduction of benzylidene functionality at C-2 as the key step. Their structures were established by high resolution NMR and Mass spectral data. The synthesized compounds have been screened against seven human cancer cell lines including ME-180 & HeLa (cervix), MCF-7, MDA-MB-453 & MDA-MB-231 (breast), PC-3 (prostate) and HT-29 (colon) using MTT assay. Most significantly, compound 10 showed potent activity against the three breast cancer cell lines. The IC₅₀ value (10.60 μM) of compound 10 against MCF-7 found to be much lower than that of the standards and parent compound. Flow cytometric analysis reveals that compound 10 arrests cell cycle in S phase and induces apoptosis in MCF cells.
Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Andhra Pradesh, India. Electronic address: uvmavadani@yahoo.com.
Uppuluri Venkata
UV
Mallavadhani
Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, Andhra Pradesh, India.
Nagi Reddy
NR
Vanga
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research, Hyderabad 5000 037, Andhra Pradesh, India.
Manish Kumar
MK
Jeengar
Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education & Research, Hyderabad 5000 037, Andhra Pradesh, India.
V G M
VG
Naidu
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009828:Oleanolic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D009828:Oleanolic Acid
Anti-cancer activity; Apoptosis; Cell cycle arrest; Oleanolic acid; Oleanolic acid hybrids