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Present results confirmed that the <i>S. grandiflora</i> used as a good antimicrobial agent in future.

Chimeric yellow fever virus 17D (YFV-17D) and dengue virus type 2 (DENV2) carrying the surface proteins of Modoc virus (MODV), a not-known-vector (NKV) flavivirus, replicated efficiently in mammalian (Vero-B) and mosquito (C6/36) cells, whereas MODV failed to replicate in mosquito cells. Transfection of C6/36 cells with MODV RNA did not result in virus replication; however, transfection of these mosquito cells with YFV-17D or DENV2 RNA did. The inability of NKV viruses (such as MODV) to infect and replicate in arthropod cells is thus not determined by the viral envelope, but by a post-entry event.

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Novel phosphoramidate derivatives of the anti-HIV nucleoside analogues AZT and d4T have been prepared by phosphorochloridate chemistry. These materials are designed to act as labile membrane-soluble prodrugs of the bio-active free nucleotides. All compounds were fully characterised by a range of methods and were subjected to evaluation in vitro of their anti-HIV efficacy. A notable feature of the current study was that any attempt to replace the amino acid moiety of the phosphoramidate with a simple amine lead to a marked, virtually total loss of activity. Such simple phenyl alkylamino phosphate derivatives of either d4T or AZT inhibit HIV replication at cytotoxic concentrations and have no detectable antiviral selectivity. This clearly highlights the vital role played by the amino acid in the antiviral efficacy of the blocked phosphoramidates.

We have previously reported the discovery and preliminary structure-activity relationships of a new class of specific HIV-1 reverse transcriptase (RT) inhibitors whose prototype compound is the 1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-3-N-[(carboxy) methyl]-thymine. In an attempt to increase the inhibitory efficacy against HIV-1 RT of this new class of nucleosides, and to further explore the structural features required for anti-HIV-1 activity, different types of modifications have been carried out on the prototype compound. These include substitution of the tert-butyldimethylsilyl groups by other liphophilic groups, replacement of the carboxy group at the N-3 position of the nucleobase by other functional groups, change in the length of the spacer between the thymine and the carboxylic acid residue and substitution of the thymine moiety by other pyrimidine (uracil, 5-ethyluracil) or purine (hypoxanthine) nucleobases. In addition, the most salient structural features of this new class of HIV-1-specific nucleosides have been incorporated into classical HIV RT nucleoside inhibitors such as ddl, AZT, d4T. Our studies demonstrate that both the carboxymethyl moiety at the nucleobase and tert-butyldimethylsilyl groups at the sugar are important structural components since deletion of either of them is detrimental to the antiviral activity.

HIV-1 reverse transcriptase (RT) plays a crucial role in the viral replication cycle, and RT inhibitors can represent a promising pathway in treating AIDS. To explore the primer grip region of HIV-1 RT, using -CH2O- as a linker, substituted benzene or pyridine rings were introduced into the left wing of diarylpyrimidines (DAPYs). A total of 17 compounds with new structures were synthesized. It showed that all compounds exhibited anti-HIV-1 (wild-type) activity values ranging from 7.6−199.0 nM. Among them, TF2 (EC50 = 7.6 nM) showed the most potent activity, which was better than that of NVP (EC50 = 122.6 nM). Notably, compared with RPV (CC50 = 3.98 μM), TF2 (CC50 > 279,329.6 nM) showed low cytotoxicity. For HIV-1 mutant strains K103N and E138K, most compounds showed effective activities. Especially for K103N, TF2 (EC50 = 28.1 nM), TF12 (EC50 = 34.7 nM) and TF13 (EC50 = 28.0 nM) exhibited outstanding activity, being superior to that of NVP (EC50 = 7495.1 nM) and EFV (EC50 = 95.1 nM). Additionally, TF2 also showed the most potent activity against E138K (EC50 = 44.0 nM) and Y181C mutant strains (EC50 = 139.3 nM). In addition, all the compounds showed strong enzyme inhibition (IC50 = 0.036−0.483 μM), which demonstrated that their target was HIV-1 RT. Moreover, molecular dynamics simulation studies were implemented to predict the binding mode of TF2 in the binding pocket of wild-type and K103N HIV-1 RT.

A series of new cyclohexenyl nucleosides is synthesized by coupling the heterocyclic bases with a protected cyclohexenyl precursor under Mitsunobu conditions. The compounds were evaluated for their antiviral and cytostatic activity. Pronounced activity against herpes simplex virus type 1 and type 2 was observed for the 2,6-diaminopurine analogue.

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.