Current Issue : July - September Volume : 2019 Issue Number : 3 Articles : 5 Articles
A series of 6-Acetyl-3-[3-Chloro-2-(Substituted)-4-Oxoazetidin-1-yl]-2, 5-Diphenyl-2, 3-Dihydropyridine-4-Carbonitrile were screened for their antifungal activity against fungi Candida albicans. These compounds have showed moderate and very good antifungal activity. The Quantitative Structure Activity-Relationships (QSAR) study on the pyridine series was made using lipophilic, electronic and steric parameters. Several statistical expressions were developed and best models were validated. The studies confirm that the antifungal activity is dependent on selected lipophilic and electronic parameters. The study suggests that substitution on R1 group with increasing lipophilic nature and decreasing electronic factor favorable for antifungal activity. The QSAR study provides important structural insights in designing of potent antimicrobial agents....
Herein, a new Ugi multicomponent reaction strategy is described to enhance activity and\nsolubility of the chemotherapeutic drug chlorambucil through its conjugation to poly(amidoamine)\n(PAMAM-NH2) dendrimers with the simultaneous introduction of lipidic (i-Pr) and cationic (â??NH2)\nor anionic (â??COOH) groups. Standard viability assays were used to evaluate the anticancer potential\nof the water-soluble dendrimers against PC-3 prostate and HT-29 colon cancer cell lines, as well\nas non-cancerous mouse NIH3T3 fibroblasts. It could be demonstrated that the anticancer activity\nagainst PC-3 cells was considerably improved when both chlorambucil and â??NH2 (cationic) groups\nwere present on the dendrimer surface (1b). Additionally, this dendrimer showed activity only\nagainst the prostate cancer cells (PC-3), while it did not affect colon cancer cells and fibroblasts\nsignificantly. The cationic chlorambucil-dendrimer 1b blocks PC-3 cells in the G2/M phase and\ninduces caspase independent apoptosis....
A rapid, high-yielding microwave-mediated synthetic procedure was developed and\noptimized using a model system of monovalent sugar linkers, with the ultimate goal of using\nthis method for the synthesis of multivalent glycoclusters. The reaction occurs between the\naldehyde/ketone on the sugars and an aminooxy moiety on the linker/trivalent core molecules used\nin this study, yielding acid-stable oxime linkages in the products and was carried out using equimolar\nquantities of reactants under mild aqueous conditions. Because the reaction is chemoselective, sugars\ncan be incorporated without the use of protecting groups and the reactions can be completed in\nas little as 30 min in the microwave. As an added advantage, in the synthesis of the trivalent\nglycoclusters, the fully substituted trivalent molecules were the major products produced in excellent\nyields. These results illustrate the potential of this rapid oxime-forming microwave-mediated reaction\nin the synthesis of larger, more complex glycoconjugates and glycoclusters for use in a wide variety\nof biomedical applications....
The chemical modification and optimization of biologically active compounds are\nessential steps in the identification of promising lead compounds for drug development. We\npreviously reported the anti-melanogenic activity of 1-(2-cyclohexylmethoxy-6-hydroxy-phenyl)-\n3-(4-hydroxymethyl-phenyl)-propenone (chalcone 21). In this study, we synthesized 21 derivatives\nof chalcone 21 and evaluated their anti-melanogenic activity in alpha -MSH-induced B16F10 cells. (E)-\nN-(4-(3-(2-(Cyclohexylmethoxy)phenyl)-3-oxoprop-1-en-1-yl)phenyl)acetamide (chalcone 21-21)\nexhibited the strongest inhibition of cellular melanin production, with an IC50 value of 0.54Micro M. It\nwas more potent than chalcone 21 and the known anti-melanogenic agents kojic acid and arbutin,\nwhose IC50 values were 4.9, 38.5, and 148.4 Micro M, respectively. Chalcone 21-21 decreased the\nexpression and activity of tyrosinase. It also decreased the expression of TRP1, TRP2 and MITF,\nthe phosphorylation of CREB and ERK1/2, and the transcriptional activity of MITF and CRE. Our\nresults demonstrate that chalcone-21-21 is an effective lead compound with anti-melanogenic\nactivity....
Enterovirus 71 (EV-A71) is the main causative pathogen of childhood hand, foot and\nmouth disease. Effective medicine is currently unavailable for the treatment of this viral disease.\nUsing the fragment-hopping strategy, a series of 2-aryl-isoindolin-1-one compounds were designed,\nsynthesized and investigated for their in vitro antiviral activity towards multiple EV-A71 clinical\nisolates (H, BrCr, Shenzhen98, Jiangsu52) in Vero cell culture in this study. The structureâ??activity\nrelationship (SAR) studies identified 2-phenyl-isoindolin-1-ones as a new potent chemotype with\npotent antiviral activity against EV-A71. Ten out of the 24 tested compounds showed significant\nantiviral activity (EC50 < 10 microM) towards four EV-A71 strains. Compounds A3 and A4 exhibited\nbroad and potent antiviral activity with the 50% effective concentration (EC50) values in the range of\n1.23â??1.76 microM. Moreover, the selectivity indices of A3 and A4 were significantly higher than those of\nthe reference compound, pirodavir. The western blotting experiment indicated that the viral VP1 was\nsignificantly decreased at both the protein and RNA level in a dose-dependent manner following\ntreatment with compound A3. Moreover, compound A3 inhibited the viral replication by acting on\nthe virus entry stage. In summary, this study led to the discovery of 2-aryl-isoindolin-1-ones as a\npromising scaffold with potent anti-EV-A71 activities, which deserves further in-depth studies....
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