Antistaphylococcal and biofilm inhibitory activities of acetyl-11-keto-β-boswellic acid from Boswellia serrata

<p>Abstract</p> <p>Background</p> <p>Boswellic acids are pentacyclic triterpenes, which are produced in plants belonging to the genus <it>Boswellia</it>. Boswellic acids appear in the resin exudates of the plant and it makes up 25-35% of the resin. β-boswellic acid, 11-keto-β-boswellic acid and acetyl-11-keto-β-boswellic acid have been implicated in apoptosis of cancer cells, particularly that of brain tumors and cells affected by leukemia or colon cancer. These molecules are also associated with potent antimicrobial activities. The present study describes the antimicrobial activities of boswellic acid molecules against 112 pathogenic bacterial isolates including ATCC strains. Acetyl-11-keto-β-boswellic acid (AKBA), which exhibited the most potent antibacterial activity, was further evaluated in time kill studies, postantibiotic effect (PAE) and biofilm susceptibility assay. The mechanism of action of AKBA was investigated by propidium iodide uptake, leakage of 260 and 280 nm absorbing material assays.</p> <p>Results</p> <p>AKBA was found to be the most active compound showing an MIC range of 2-8 μg/ml against the entire gram positive bacterial pathogens tested. It exhibited concentration dependent killing of <it>Staphylococcus aureus </it>ATCC 29213 up to 8 × MIC and also demonstrated postantibiotic effect (PAE) of 4.8 h at 2 × MIC. Furthermore, AKBA inhibited the formation of biofilms generated by <it>S. aureus </it>and <it>Staphylococcus epidermidis </it>and also reduced the preformed biofilms by these bacteria. Increased uptake of propidium iodide and leakage of 260 and 280 nm absorbing material by AKBA treated cells of <it>S aureus </it>indicating that the antibacterial mode of action of AKBA probably occurred via disruption of microbial membrane structure.</p> <p>Conclusions</p> <p>This study supported the potential use of AKBA in treating <it>S. aureus </it>infections. AKBA can be further exploited to evolve potential lead compounds in the discovery of new anti-Gram-positive and anti-biofilm agents.</p

Boswellic acids: a group of medicinally important compounds

This review, containing over 276 references, covers the progress made in the chemistry and bioactivity of this important group of triterpenoids. Though initially known for their anti-inflammatory and antiarthritic activities through a unique 5-LO inhibition mechanism, boswellic acids have recently attained significance due to their anti-cancer properties. The phytochemistry and chemical modifications, including mechanism of action, are discussed

Synthesis of Biaryls via Benzylic C–C Bond Cleavage of Styrenes and Benzyl Alcohols

A metal-free oxidative coupling of styrenes and benzyl alcohols with arenes has been developed for the synthesis of biaryls. The reaction features a conspicuous benzylic C–C bond cleavage of styrenes and benzyl alcohols. The reaction with both substrates proceeds through a common aldehydic intermediate formed through oxidative C–C bond cleavage of alkene and oxidation of benzyl alcohols. The reaction proceeds efficiently over a broad range of substrates with excellent functional group tolerance

A general metal-free approach for the stereoselective synthesis of C-glycals from unactivated alkynes

A novel metal-free strategy for a rapid and α-selctive C-alkynylation of glycals was developed. The reaction utilizes TMSOTf as a promoter to generate in situ trimethylsilylacetylene for C-alkynylation. Thanks to this methodology, we can access C-glycosides in a single step from a variety of acetylenes , i.e., arylacetylenes and most importantly aliphatic alkynes

A facile approach towards enantiomerically pure masked β-amino alcohols

b-Amino alcohols are bioactive molecules, used also as catalysts in asymmetric C–C bond formation. While asymmetric synthesis has been the preferred route for their preparation, there was always been a need to develop a facile methodology involving environmentally friendly transformations. Masked amines in the form of phthalimide alcohols, prepared via a fast coupling reaction in an ionic liquid as a reusable reaction media together with reduction and an efficient biocatalytic resolution, offer a green methodology for enantiomerically pure products(ee . 99%, 50 g L21)

A comparative study of proapoptotic potential of cyano analogues of boswellic acid and 11-keto-boswellic acid

Semi-synthetic analogues of b-boswellic acid (BA) and 11-keto-b-boswellic acid (KBA) were comparatively evaluated for in vitro cytotoxicity against human myeloid leukaemia (HL-60) and human cervical carcinoma (HeLa) cells. 2-Cyano analogues of both the triterpenes were observed to have significant cytotoxicity against both the cells, displaying cytotoxicity in HL-60 cells at low concentrations. Further investigations suggested the proapoptotic potential associated with the two molecules to induce cytotoxicity in HL-60 cells, where one of them showed early proapoptotic effect as evidenced by several biological end-points of the apoptosis such as annexinV binding, DNA fragmentation and increase in sub-G0 DNA fraction and apoptotic bodies formation (Hoechst 33258 staining and SEM studies)

Cladosporol A triggers apoptosis sensitivity by ROS-mediated autophagic flux in human breast cancer cells

Abstract Background Endophytes have proven to be an invaluable resource of chemically diverse secondary metabolites that act as excellent lead compounds for anticancer drug discovery. Here we report the promising cytotoxic effects of Cladosporol A (HPLC purified >98%) isolated from endophytic fungus Cladosporium cladosporioides collected from Datura innoxia. Cladosporol A was subjected to in vitro cytotoxicity assay against NCI60 panel of human cancer cells using MTT assay. We further investigated the molecular mechanism(s) of Cladosporol A induced cell death in human breast (MCF-7) cancer cells. Mechanistically early events of cell death were studied using DAPI, Annexin V-FITC staining assay. Furthermore, immunofluorescence studies were carried to see the involvement of intrinsic pathway leading to mitochondrial dysfunction, cytochrome c release, Bax/Bcl-2 regulation and flowcytometrically measured membrane potential loss of mitochondria in human breast (MCF-7) cancer cells after Cladosporol A treatment. The interplay between apoptosis and autophagy was studied by microtubule dynamics, expression of pro-apoptotic protein p21 and autophagic markers monodansylcadaverine staining and LC3b expression. Results Among NCI60 human cancer cell line panel Cladosporol A showed least IC50 value against human breast (MCF-7) cancer cells. The early events of apoptosis were characterized by phosphatidylserine exposure. It disrupts microtubule dynamics and also induces expression of pro-apoptotic protein p21. Moreover treatment of Cladosporol A significantly induced MMP loss, release of cytochrome c, Bcl-2 down regulation, Bax upregulation as well as increased monodansylcadaverine (MDC) staining and leads to LC3-I to LC3-II conversion. Conclusion Our experimental data suggests that Cladosporol A depolymerize microtubules, sensitize programmed cell death via ROS mediated autophagic flux leading to mitophagic cell death. Graphical abstract The proposed mechanism of Cladosporol A -triggered apoptotic as well as autophagic death of human breast cancer (MCF-7) cells. The figure shows that Cladosporol A induced apoptosis through ROS mediated mitochondrial pathway and increased p21 protein expression in MCF-7 cells in vitro

Structure–activity relationship (SAR) of parthenin analogues with pro-apoptotic activity: Development of novel anti-cancer leads

Analogues of parthenin were synthesized by substitutions at different reaction centres to establish a structure–activity relationship (SAR). Some of the molecules have displayed significant cytotoxicity in human cervical carcinoma (HeLa) and human myeloid leukemia (HL-60) cells. A few of the compounds also induced apoptosis in HL-60 cells measured in terms of sub-Go/G1 DNA fraction. Also one of the lead molecules has been shown to be the inhibitor of both telomerase and topoisomerase-II