5 totally different endophytic fungal species were isolated from bark and leaf parts of Calophyllum inophyllum. Leaf part yielded Trichoderma harzianum and Alternaria species, whereas bark showed the presence of Fusar...5 totally different endophytic fungal species were isolated from bark and leaf parts of Calophyllum inophyllum. Leaf part yielded Trichoderma harzianum and Alternaria species, whereas bark showed the presence of Fusarium species, Aspergillus species and unidentified fungi. Two solvents (hexane and methanol) were used for endophytic fungal extraction and the Alternaria species had shown the presence of coumarin whereas Trichoderma harzianum in methanol extract and Fusarium species in hexane extract had shown the coumarin(s) in all the four methods tested. The total coumarin yield was more in microwave assistance method, the methanol Alternaria species (3.941 ± 0.082) stood first, followed by hexane extract of Alternaria species (3.254 ± 0.082), Fusarium species (2.532 ± 0.082) and Trichoderma harzianum (2.294 ± 0.082), the plant extract showed 4.149 + 0.053. The methanol extract of Alternaria species inhibited the activity of HIV-Reverse Transcriptase (RT) (82.81 ± 1.0), integrase (98%) and protease (78) in maximum level followed by hexane extract of Alternaria species (71.12 ± 0.9, 89, 68), Fusarium species (63.92 ± 1.8, 67, 66) and Trichoderma harzianum (56.69 ± 0.9, 71, 63). The endophytic fungi Alternaria species inhibited all the three viral enzymes at maximum level and it was more than standard drug. However, in order to know possible anti-HIV, it is necessary to isolate active coumarin from the Alternaria species and the mechanism of action will be studied in future studies.展开更多
A series of novel dinucleosides linked by s-triazine were synthesized via the nucleophilic substitution reaction of amino nucleoside and cyanuric chloride in THF/H20. The biological activities of these novel dinucleos...A series of novel dinucleosides linked by s-triazine were synthesized via the nucleophilic substitution reaction of amino nucleoside and cyanuric chloride in THF/H20. The biological activities of these novel dinucleoside analogs against HIV-RT, HeLa and A-549 cell lines in vitro were evaluated.展开更多
The results of computer simulations of the binding of etravirine (TMC125) and rilpivirine (TMC278) to HIV reverse transcriptase are reported. It is confirmed that consistent binding free energy estimates are obtained ...The results of computer simulations of the binding of etravirine (TMC125) and rilpivirine (TMC278) to HIV reverse transcriptase are reported. It is confirmed that consistent binding free energy estimates are obtained with or without the application of torsional restraints when the free energies of imposing the restraints are taken into account. The restraints have a smaller influence on the thermodynamics and apparent kinetics of binding of TMC125 compared to the more flexible TMC278 inhibitor. The concept of the reorganization free energy of binding is useful to understand and categorize these effects. Contrary to expectations, the use of conformational restraints did not consistently enhance convergence of binding free energy estimates due to suppression of binding/unbinding pathways and due to the influence of rotational degrees of freedom not directly controlled by the restraints. Physical insights concerning the thermodynamic driving forces for binding and the role of “jiggling” and “wiggling” motion of the ligands are discussed. Based on these insights we conclude that an ideal inhibitor, if chemically realizable, would possess the electrostatic charge distribution of TMC125, so as to form strong interactions with the receptor, and the larger and more flexible substituents of TMC278, so as to minimize reorganization free energy penalties and the effects of resistance mutations, suitably modified, as in TMC125, so as to disfavor the formation of non-binding competent extended conformations when free in solution.展开更多
文摘5 totally different endophytic fungal species were isolated from bark and leaf parts of Calophyllum inophyllum. Leaf part yielded Trichoderma harzianum and Alternaria species, whereas bark showed the presence of Fusarium species, Aspergillus species and unidentified fungi. Two solvents (hexane and methanol) were used for endophytic fungal extraction and the Alternaria species had shown the presence of coumarin whereas Trichoderma harzianum in methanol extract and Fusarium species in hexane extract had shown the coumarin(s) in all the four methods tested. The total coumarin yield was more in microwave assistance method, the methanol Alternaria species (3.941 ± 0.082) stood first, followed by hexane extract of Alternaria species (3.254 ± 0.082), Fusarium species (2.532 ± 0.082) and Trichoderma harzianum (2.294 ± 0.082), the plant extract showed 4.149 + 0.053. The methanol extract of Alternaria species inhibited the activity of HIV-Reverse Transcriptase (RT) (82.81 ± 1.0), integrase (98%) and protease (78) in maximum level followed by hexane extract of Alternaria species (71.12 ± 0.9, 89, 68), Fusarium species (63.92 ± 1.8, 67, 66) and Trichoderma harzianum (56.69 ± 0.9, 71, 63). The endophytic fungi Alternaria species inhibited all the three viral enzymes at maximum level and it was more than standard drug. However, in order to know possible anti-HIV, it is necessary to isolate active coumarin from the Alternaria species and the mechanism of action will be studied in future studies.
基金Projected supported by the National Basic Research 973 Pre-research Program of China （No. 2010CB534913）, the National Natural Science Foundations of China （NSFC） （Nos. 20672027 and 20972039）, the Natural Science Foundations of Hebei Province （No. B2008000588） and the program of Science and Technology （S ＆ T） of Hebei Province （No. 09276418D-13）.
文摘A series of novel dinucleosides linked by s-triazine were synthesized via the nucleophilic substitution reaction of amino nucleoside and cyanuric chloride in THF/H20. The biological activities of these novel dinucleoside analogs against HIV-RT, HeLa and A-549 cell lines in vitro were evaluated.
文摘The results of computer simulations of the binding of etravirine (TMC125) and rilpivirine (TMC278) to HIV reverse transcriptase are reported. It is confirmed that consistent binding free energy estimates are obtained with or without the application of torsional restraints when the free energies of imposing the restraints are taken into account. The restraints have a smaller influence on the thermodynamics and apparent kinetics of binding of TMC125 compared to the more flexible TMC278 inhibitor. The concept of the reorganization free energy of binding is useful to understand and categorize these effects. Contrary to expectations, the use of conformational restraints did not consistently enhance convergence of binding free energy estimates due to suppression of binding/unbinding pathways and due to the influence of rotational degrees of freedom not directly controlled by the restraints. Physical insights concerning the thermodynamic driving forces for binding and the role of “jiggling” and “wiggling” motion of the ligands are discussed. Based on these insights we conclude that an ideal inhibitor, if chemically realizable, would possess the electrostatic charge distribution of TMC125, so as to form strong interactions with the receptor, and the larger and more flexible substituents of TMC278, so as to minimize reorganization free energy penalties and the effects of resistance mutations, suitably modified, as in TMC125, so as to disfavor the formation of non-binding competent extended conformations when free in solution.
