Design, synthesis, anti-inflammatory, cytotoxic and cell based studies of some novel side chain analogues of myrrhanones A & B isolated from the gum resin of Commiphora mukul.

Myrrhanones A (1) and B (2), isolated from the gum resin of Commiphora mukul, were reported to exhibit anticancer and anti-inflammatory activities. In view of their interesting skeletal features and biological activities they have been chemically modified by exploiting their side chain functionalities to synthesise 29 diverse analogues. All the synthesized analogues were screened for their cytotoxic potential against a panel of five human cancer cell lines which include DU145 (Prostate), HT-29 (Colon), MCF-7 (Breast), Hela (Cervical) and U87MG (Glioblastoma) along with a normal cell line (L132). The synthesized analogues were also screened for anti-inflammatory activity against TNF-α and IL-1ß using LPS induced inflammation model employing U937 cells. The biological screening results revealed that compounds 4b (piperidine analogue), 9d (linear aliphatic four member amide analogue) and 9i (N-methyl piperazine analogue) displayed significant cytotoxic activity against MCF-7, HT-29 and DU145 [IC50 (µM): 4.65 ±â€¯1.28, 5.48 ±â€¯0.13 and 6.63 ±â€¯1.39] respectively. These analogues were further taken up for apoptotic assay, which confirmed that compounds 4b, 9d and 9i induced apoptosis in MCF-7, HT-29, DU145 cells and arrested in G0/G1 phase. Further, compounds 9c and 9g found to exhibit good anti-inflammatory activity against TNF-α with IC50 (µM) values of 10.02 ±â€¯2.13 and 10.53 ±â€¯0.48 respectively, while compound 2 exhibited strong inhibitory activity against both TNF-α (IC50: 9.39 ±â€¯0.44 µM) and IL-1ß (IC50: 12.15 ±â€¯1.36 µM).

Novel triazole hybrids of myrrhanone C, a natural polypodane triterpene: Synthesis, cytotoxic activity and cell based studies.

The 3-keto functionality in ring A of myrrhanone C, a natural bicyclic triterpene has been chemically modified and synthesized 27 novel triazole hybrids belonging to two different series in very good to excellent yields (66-83%). The synthesized compounds were thoroughly characterized by their spectroscopic data (IR, (1)H&(13)C NMR, HRMS). All the synthesized compounds were evaluated for their cytotoxic potential against a panel of five human cancer cell lines by employing MTT assay using doxorubicin as the standard. In general the synthesized compounds showed anticancer activity against almost all the cell lines screened. Interestingly, the oxime based triazoles (4a-4n) showed higher activity than the benzylidene triazoles (6a-6m). Most significantly compound 4a showed potent activity against all the tested cell lines, especially against lung cancer (A-549) with an IC 50 of 6.16 µm. In view of their significant activity against lung cancer cell lines, compounds 4a and 4l were subjected to detailed biological studies, which revealed that they arrested cell cycle in G2/M phase and induced cell death by apoptosis that was further confirmed by Hoechst staining, measurement of mitochondrial membrane potential (ΔΨm) and Annexin V-FITC assay. These compounds will serve as lead molecules in the development of potent anticancer drug candidates especially for lung cancer.

Synthesis and anticancer activity of novel fused pyrimidine hybrids of myrrhanone C, a bicyclic triterpene of Commiphora mukul gum resin.

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.