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.

Pyrimidine: a review on anticancer activity with key emphasis on SAR

“…141a (IC 50 = 9.5 μM) and 141b (IC 50 = 7.7 μM) showed the best activity against A-549 cancer cell line due to induction of apoptosis at the G0/G1 phase of the cell cycle. SAR suggested that 4chloro and 4-bromo pyrimidine hybrid have 5-6 times more activity against the A-549 whereas 2-3 times more activity against the other abovementioned cell lines than the parent compound [144]. Novel azacalix [2]aren e [2] pyrimidines were screened against the MCF-7 cancer cell line.…”

New Hybrids Derived from Podophyllic Aldehyde and Diterpenylhydroquinones with Selectivity toward Osteosarcoma Cells

“…In this context, natural products are promising and efficient starting materials for the discovery and development of new drugs, particularly in the anticancer field; more than 70% of the current anticancer drugs are natural or derived of natural products with a variety of structures and mechanisms of action that would increase when they are combined into new hybrid entities . The synergistic or additive effect of those new chemical entities is a promising approach in diverse diseases, particularly in cancer therapy, − for example, to avoid resistances or discover new applications for future treatments …”

Modeling of Anticancer Sulfonamide Derivatives Lipophilicity by Chemometric and Quantitative Structure-Retention Relationships Approaches

“…The anticancer potential against the HCT-116 cell line has also been demonstrated by N-acylated benzenesulfonamides, which contained at the benzene ring the 1-naphthylmethylthio substituent and the sulfonamidic nitrogen atom bonded to acetic acid or cinnamic acid residues [30]. Similarly, fused pyrimidine hybrids of myrrhanone C and Argentatins A-C showed noticeable anticancer activity against several human cancer cell lines [31,32]. The main goal of this study was to assess the sulfonamide derivatives with proven anticancer activities against human colon cancer (HCT-116) using a chromatographic approach.…”