Search

Since time immemorial Boswellia serrata has been a useful traditional plant and its oleo-gum-resin is regularly used as an important constituent in herbal medicines for inflammation, cancer sufferers and cosmetics. This study focuses on the antibacterial and anticancer activities of B. serrata oleo-gum-resin extract, fractions and isolates. Time kill kinetic assay, combination study and ethidium bromide efflux pump inhibitory assay of the leading molecule 3-hydroxy-11-keto- β -boswellic acid (KBA) have been evaluated. The extract, fractions and the isolated molecule have shown anti-proliferative activity in different cancer cell lines, and the inhibition ranged from 13% to 93%. KBA caused anti-proliferative dose-dependent impacts on all human malignant cells (IC 50 4.10–37.9 µg/ml). In antibacterial study of the extract, fractions and isolated molecules have shown minimum inhibitory concentration MIC range from 31.25 to 1000 μg/ml against 8 different Gram-positive and Gram-negative bacterial strains. KBA exhibited synergistic effect with a oxacillin against different drug resistant clinical isolates with fractional inhibitory concentration index (FICI) in the range of 0.325–0.450 µg/ml. KBA exhibited bacteriostatic killing mechanism and could also modulate ethidium bromide efflux pump to find its potential in combination therapy against multi-drug resistant Staphylococcal infections. KBA in the extract was quantified using HPLC-PDA and its structure was validated for the first time by X-ray crystallography. This study reinforced the promising treatment of KBA for cancer and S. aureus infections. KBA can be further explored to develop potential lead combinations of anti-cancer and anti-Gram-positive bacterial herbal formulations. [Display omitted] • Structure of KBA (3-hydroxy-11-keto- β -boswellicacid) is confirmed by X-ray crystallography. • KBA displayed antiproliferative impact on human malignant cells (IC 50 : 4.1–37.9 µg/ml). • KBA has shown MIC (31.25–1000 μg/ml) against Gram-(+) and Gram-(-) bacterial strains. • KBA is effective against drug resistant clinical isolates with FICI of 0.32–0.45 µg/ml. [ABSTRACT FROM AUTHOR]

[Display omitted] Receptors are proteinous macromolecules which remain in the apo form under normal/unliganded conditions. As the ligand approaches, there are specific stereo-chemical changes in the apo form of the receptor as per the stereochemistry of a ligand. Accordingly, a series of substituted dimethyl-chroman-based stereochemically flexible and constrained Tamoxifen analogs were synthesized as anti-breast cancer agents. The synthesized compounds 19a-e, 20a-e, 21, and 22a-e, showed significant antiproliferative activity against estrogen receptor-positive (ER+, MCF-7) and negative (ER-, MDA MB-231) cells within IC 50 value 8.5–25.0 µM. Amongst all, four potential molecules viz 19b , 19e , 22a , and 22c , were evaluated for their effect on the cell division cycle and apoptosis of ER+ and ER- cancer cells (MCF-7 & MDA MB-231cells), which showed that these compounds possessed antiproliferative activity through triggering apoptosis. In-silico docking experiments elucidated the possible affinity of compounds with estrogen receptors-α and -β. [ABSTRACT FROM AUTHOR]

Abstract: Two new naturally occurring sesquiterpenes (1 and 3) along with a known sesquiterpene (2) were isolated from Vitex negundo L. stem. 13C NMR data of 2 are also reported in the present study as it was not reported. Structures of compounds were elucidated by NMR spectroscopy and their stereochemistries were established by X-ray diffraction. [Copyright &y& Elsevier]

Ent -labdane-related diterpene ( ent -LRD) specialized (i.e. secondary) metabolites of the medicinal plant kalmegh ( Andrographis paniculata ) have long been known for several pharmacological activities. However, our understanding of the ent -LRD biosynthetic pathway has remained largely incomplete. Since ent -LRDs accumulate in leaves, we carried out a comparative transcriptional analysis using leaf and root tissues, and identified 389 differentially expressed transcripts, including 223 transcripts that were preferentially expressed in leaf tissue. Analysis of the transcripts revealed various specialized metabolic pathways, including transcripts of the ent -LRD biosynthetic pathway. Two class II diterpene synthases ( ApCPS1 and ApCPS2 ) along with one ( ApCPS1 ′) and two ( ApCPS2′ and ApCPS2 ″) transcriptional variants that were the outcomes of alternative splicing of the precursor mRNA and alternative transcriptional termination , respectively, were identified. ApCPS1 and ApCPS2 encode for 832- and 817-amino acids proteins, respectively, and are phylogenetically related to the dicotyledons ent -copalyl diphosphate synthases ( ent -CPSs). The spatio-temporal patterns of ent -LRD metabolites accumulation and gene expression suggested a likely role for ApCPS1 in general (i.e. primary) metabolism, perhaps by providing precursor for the biosynthesis of phytohormone gibberellin (GA). However, ApCPS2 is potentially involved in tissue-specific accumulation of ent -LRD specialized metabolites. Bacterially expressed recombinant ApCPS2 catalyzed the conversion of (E,E,E)-geranylgeranyl diphosphate (GGPP), the general precursor of diterpenes to ent -copalyl diphosphate ( ent -CPP), the precursor of ent -LRDs. Taken together, these results advance our understanding of the tissue-specific accumulation of specialized ent -LRDs of medicinal importance. [ABSTRACT FROM AUTHOR]

Diosgenin has been modified to furostane derivatives after opening the F-spiroacetal ring. The aldehyde group at C26 in derivative 8 was unexpectedly transformed to the ketone 9. The structure of ketone 9 was confirmed by spectroscopy and finally by X-ray crystallography. Five of the diosgenin derivatives showed significant anticancer activity against human cancer cell lines. The most potent molecule of this series i.e. compound 7, inhibited cellular growth by arresting the population at G0/G1 phase of cell division cycle. Cells undergo apoptosis after exposure to the derivative 7 which was evident by increase in sub G0 population in cell cycle analysis. Docking experiments showed caspase-3 and caspase-9 as possible molecular targets for these compounds. This was further validated by cleavage of PARP, a caspase target in apoptotic pathway. Compound 7 was found non-toxic up to 1000mg/kg dose in acute oral toxicity in Swiss albino mice. [ABSTRACT FROM AUTHOR]