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• Novel pentacyclic triterpene amides (3a-3l) and 1 H -1,2,3-triazole analogues (5a-5k) of β -AKBA were synthesized from β -AKBA. • All the compounds were screened against the breast cancer cell line (MDA-MB-231). • Compounds 5a and 5i were found more potent than β -AKBA. • The X-ray single crystal of compound 3a was developed and studied. • The in-silico study was performed to see the binding efficacy of the active compounds. In this work, we describe the synthesis of 12 new pentacyclic triterpene amides (3a-3l) and 11 new 1 H -1,2,3-triazole analogues (5a-5k) of 3- O -acetyl-11-keto- β -boswellic acid (β -AKBA) and evaluated them for their human breast cancer (MDA-MB-231) growth inhibitory activities. The resulting compounds were characterized by 1H NMR, 13C NMR, and HR-ESI-MS spectroscopy. X-ray crystallography unambiguously confirmed the exact structure of compound 3a. The cytotoxic potential of the synthesized compounds was scrutinized against triple-negative breast cancer (MDA-MB-231) and normal (MCF-10A) cell lines. Furthermore, all the synthesized derivatives exhibited significant anti-proliferative activities with IC 50 values ranging from 8.1 ± 0.2 to 18.5 ± 0.4 μM. Among them, compounds 5a and 5i exhibited noteworthy activities and were several times more potent than the parent compound β -AKBA. Furthermore, molecular docking analysis predicted that these molecules exhibit their anti-proliferative effects by binding to the folate receptor alpha (FRα). Overall, this new study may pave the way to medicinal analogues of β -AKBA as anti-breast cancer agents. [Display omitted] [ABSTRACT FROM AUTHOR]

This study aimed to compare the effect of Boswellic acid derivatives on the viability, apoptosis, and epigenomic profiling of breast cancer. According to the viability assays, 3-O-acetyl-11-keto-β-Boswellic acid (AKBA) showed more toxicity against MDA-MB-231 cells when compared with the 3-O-acetyl-β-Boswellic acid (ABA). In contrast, ABA revealed less toxicity against MCF-10A. Cell cycle and apoptosis assays determined the maximum apoptotic effect of AKBA on MCF-7, and MDA-MB-231 cells. Interestingly, β-Boswellic acid (BA) and ABA did not promote the apoptosis in MCF-10A cells. Transwell migration assay indicated the greatest normalized inhibition (around 160%) in the migration of MDA-MB-231 cells induced by AKBA. The expression of P53, BAX, and BCL2 genes in cancerous cell lines has affirmed that both AKBA and ABA could induce the maximal apoptosis. Western-blot investigation demonstrated that the maximum over-expression of P53 protein (1.96 times) was caused by AKBA in MDA-MB-231 cells, followed by ABA in MCF-7 cells. The BCL2 protein expression was in agreement with the previously reported results. The global DNA methylation in both cancerous cells was reduced by ABA. These results suggest that ABA represented more epigenetic modulatory effect while AKBA shows more cytotoxic and apoptotic effect against breast cancer cell lines. [ABSTRACT FROM AUTHOR]

A new a bisflavan-3-ol, boerhavianane (1), was isolated from Boerhavia elegans L. The structure of the flavanol dimer was elucidated by detailed spectroscopic analysis including 1H, 13C NMR, COSY, HMQC, HMBC, and ESI-MS. Boerhavianane (1) was evaluated for its anticancer activity and demonstrated a significant reduction in the viability of breast cancer cells in a concentration-dependent manner with an IC50 value of 38.48 μg/mL. Moreover, boerhavianane (1) was also screened for DPPH antioxidant activity and acetyl cholinesterase, xanthine oxidase, urease, and α-glucosidase enzyme inhibition activities. Preliminary results showed that it exhibited significant inhibition (81.0 ± 2.0%) against urease enzyme, whereas for DPPH radical scavenging it showed moderate activity (75.0 ± 1.5%). [ABSTRACT FROM AUTHOR]

• Sixteen new analogues (3 – 8, 10a-j) of β-AKBA and β-ABA were synthesized. • The cytotoxic potential of the synthesized compounds was scrutinized against the triple-negative breast cancer (MDA-MB-231) and normal cell lines (MCF-10A). • Interestingly, all the synthesized derivatives exhibited highly potent anti-proliferative activity with IC 50 values in range of 4.45 to 14.45 µM. • Compounds 10f, 10i and 10j exhibited exceptional inhibitory potency and found several times more potent than the parent compounds 1 and 2. • The compounds 5 and 6 were sustained by X-ray crystallography, while molecular docking of the active compounds was also performed A series of new analogues of 3- O -acetyl-11-keto- β -boswellic acid (β -AKBA, 1), 3- O -acetyl- β -boswellic acid (β -ABA, 2) (3–8) and 1 H -1,2,3-triazole hybrids of β -AKBA (10a-j) were synthesized by employing highly efficient "Click" chemistry reaction protocol. All synthesized compounds were characterized by 1H-, 13C NMR, and HRMS spectroscopy. The structures of compounds 5 and 6 were unambiguously confirmed by the single crystal X-ray analysis diffraction method. The cytotoxic potential of the synthesized compounds was scrutinized against the triple-negative breast cancer (MDA-MB-231) and normal (MCF-10A) cell lines. Furthermore, all the synthesized derivatives exhibited highly potent anti-proliferative activity with IC 50 values ranging from 4.45 to 14.45 µM. Among them, compounds 10j, 10f, and 10i exhibited exceptional inhibitory potency and were found several times more potent than the parent compounds 1 and 2. Additionally, the cheminformatics method was used to identify the potential drug target of the most potent compounds (10j, 10f, and 10i) and their binding mechanism with the selected drug target was predicted through molecular docking. The combined 2D-similarity searching, and structure-based binding investigation predict that these compounds can target CHK1 to produce anti-cancer effects in TNBC. This study lays a good foundation for new triterpenic triazole analogues of boswellic acids and could be effective anticancer leads in breast cancer therapeutics. [ABSTRACT FROM AUTHOR]

Bio-guided fractionation of the guggul gum resin of Commiphora mukul HOOK using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay for the breast cancer cell line MDA-MB-231 led to the isolation of a new C17 norditerpene named myrrhanone C ( 1) along with two known polypodane-type triterpenes, namely, myrrhanone B ( 2) and myrrhanol B ( 3). The structures of the isolated compounds were elucidated by means of 1D (1H and 13C) and 2D (correlation spectroscopy, heteronuclear single-quantum coherence, heteronuclear multiple-bond correlation, and nuclear Overhauser effect spectroscopy) NMR spectroscopy as well as mass (electrospray ionization-mass spectroscopy) spectral analyses. Interestingly myrrhanone C ( 1) was able to induce a substantial decline in cell proliferation. It reduced the viability of cancer cells by almost 81% and 87% at concentrations of 50 and 100 μg mL−1, respectively. Myrrhanone B ( 2) and myrrhanol B ( 3) showed a concentration-dependent growth inhibitory effect on cancer cells, with the latter being slightly more cytotoxic than the former at both the concentrations tested. Furthermore, myrrhanone C ( 1) and myrrhanone B ( 2) showed good α-glucosidase and urease inhibition. [ABSTRACT FROM AUTHOR]