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Abstract For Abstract see ChemInform Abstract in Full Text.

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.

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.

A series of 4-(naphthalen-1-yl)-1,2,5-thiadiazol-3-hydroxyl derivatives (Ia-Im and IIa-IIe) designed as novel HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) was synthesized via an expeditious route and evaluated for their anti-HIV activities in MT-4 cell cultures. All the synthesized compounds were structurally confirmed by spectral analyses. Biological results showed that three analogues displayed moderate inhibitory activity against wild-type (wt) HIV-1 replication with EC(50) values ranging from 16 to 22 μm. Molecular docking of compound Ih with wt HIV-1 RT was performed to understand the binding mode between these inhibitors and the wt HIV-1 RT and to rationalize some SARs.

The development of new non-nucleoside reverse transcriptase inhibitors (NNRTIs) is an efficient strategy for finding new therapeutic agents against human immunodeficiency virus (HIV). A large number of 6-substituted uracil derivatives have been prepared in order to explore new NNRTIs. However, there are few approaches to anti-HIV agents from 1,3-disubstituted uracil derivatives. Therefore, we tried to prepare several 1,3-disubstituted uracils, which were easily obtainable from uracil by preparation under alkali and Mitsunobu conditions, and examined their antiviral activity against HIV-1 and human cytomegalovirus (HCMV). We found that 1-benzyl-3-(3,5-dimethylbenzyl)uracil and 1-cyanomethyl-3-(3,5-dimethylbenzyl)-4-thiouracil showed powerful inhibition against HCMV and HIV-1, respectively.

Beginning with 3-cyclopenten-1-ylamine hydrochloride, the 5'-nor derivatives of carbocyclic 2'-deoxyguanosine (2), 2'-deoxyadenosine (3), and 2,6-diaminopurine 2'-deoxyribofuranoside (4) have been prepared. These compounds were evaluated for antiviral potential versus herpes simplex virus, varicella-zoster virus, cytomegalovirus, vaccinia virus, vesicular stomatitis virus, and human immunodeficiency virus and found to lack activity. Also, compounds 2-4 were virtually nontoxic toward the host (human diploid fibroblast ESM and HEL) cells. These biological properties may be due to the inability of 2-4 to be phosphorylated to the requisite nucleotide level that is likely to be necessary for biological activity by correlation to carbocyclic 2'-deoxyguanosine (1), which possesses significant antiviral properties as a result of conversion to its 5'-triphosphate derivative.

In the search for antitumor active metal complexes several ruthenium complexes have been reported to be promising. A series of mononuclear Ru(II) complexes, [Ru(T)2(S)]2+, where T = 2,2′-bipyridine/1,10-phenanthroline and S = CH3-bitsz, Cl-bitsz, Br-bitsz, tmtsz, dmtsz, have been prepared and characterized by UV-Vis, IR, 1H-NMR, FAB-mass spectroscopy, and elemental analysis. The complexes were subjected to in vivo anticancer activity against a transplantable murine tumor cell line Ehrlich's ascitic carcinoma (EAC) and in vitro cytotoxic activity against human cancer cell line Molt 4/C8, CEM, and murine tumor cell line L1210. Ruthenium complexes showed promising biological activity especially in decreasing tumor volume and viable ascitic cell counts. Treatment with these complexes prolonged the life span of EAC-tumor-bearing mice by 10–48%. In vitro evaluation of these ruthenium complexes revealed cytotoxic activity from 0.21 to 24 µmol L−1 against Molt 4/C8, 0.16–19 µmol L−1 against CEM, and 0.75–32 µmol L−1 against L1210 cell proliferation, depending on the nature of the compound.

HIV protease is a promising drug target for AIDS therapy, and several potent HIV-1 protease inhibitors have been reported to date. Although existing inhibitors exhibit high selectivity, they have also been associated with severe side effects and the possible emergence of therapeutic resistance. As HIV protease cleaves the peptide bond via a tetrahedral intermediate, various transition-state models such as hydroxyethylamine (HEA) have been designed. We therefore pursued an efficient synthesis of an HEA isostere; this was performed with a novel one-pot reduction-transimination-reduction reaction sequence as a key step. α-Aminophosphonate and phosphoramidate derivatives of the HEA isostere were designed and synthesized, and all of the synthesized derivatives were assayed for their anti-HIV activities against wild-type and mutant HIV strains. Phosphoramidate derivative 15 a was found to be the most active of all synthesized compounds against the III(B) and RES056 strains. As phosphonates are known to exhibit physiological stability, good cell permeability, and other promising pharmacokinetic characteristics, our newly synthesized compounds have the potential as alternatives to existing therapeutics and diagnostics.