title: Synthesis and anticancer activity of novel fused pyrimidine hybrids of myrrhanone C, a bicyclic triterpene of Commiphora mukul gum resin.
abstract: Myrrhanone C [8(R)-3-oxo-8-hydroxypolypoda-13E,17E,21-triene], a bicyclic triterpene isolated from the gum resin of Commiphora mukul, has been chemically transformed to synthesize a series of ten novel pyrimidine hybrids in good to excellent yields. The synthesized compounds (2-22) were evaluated for their anticancer potential against a panel of six cancer cell lines, namely A-549 (lung), Hela (cervical), MCF-7 (breast), ACHN (renal), Colo-205 (colon) and B-16 (mouse melanoma) by employing the MTT assay. In general, the synthesized compounds showed significant anticancer activity against all the cancer cell lines tested. Interestingly, the pyrimidine hybrids 18 and 19 showed good activity against the A-549, MCF-7, B-16, Colo-205 and ACHN cancer cell lines with [Formula: see text] values between 7.7-37.8 [Formula: see text]M. Most significantly, compounds 19 (IC[Formula: see text]: 7.7 [Formula: see text]M) and 18 (IC[Formula: see text]: 9.5 [Formula: see text]M) showed about five- and six-fold enhanced activities, respectively, compared to the parent myrrhanone C (1) against A-549 cell line. Flow cytometric analysis revealed that compounds 18 and 19 induced apoptosis in A-549 cells and arrested the cell growth in the G0/G1 phase.
authors.affiliation: Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India. uvmavadani@yahoo.com.
authors.forename: Uppuluri Venkata
authors.initials: UV
authors.lastname: Mallavadhani
authors.affiliation: Natural Products Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
authors.forename: Madasu
authors.initials: M
authors.lastname: Chandrashekhar
authors.affiliation: Department of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India.
authors.forename: Vadithe Lakshma
authors.initials: VL
authors.lastname: Nayak
authors.affiliation: Department of Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India. sistla@iict.res.in.
authors.forename: Sistla
authors.initials: S
authors.lastname: Ramakrishna
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D029744:Commiphora / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D012116:Resins, Plant / Q000737:chemistry; D014315:Triterpenes / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D011743:Pyrimidines; D012116:Resins, Plant; D014315:Triterpenes
keywords: Anticancer activity; Apoptosis; Cell cycle arrest; Hybrids; Myrrhanone C; Pyrimidines