Synthesis and anti‐HIV activity of new 2‐thiolumazine and 2‐thiouracil metal complexes

Abstract

A series of new Cu(II), Pt(II), VO(II), Fe(II), and Co(II) complexes (1‐‐5) with 3‐methyl‐6,7‐diphenyllumazine are described. Similarly, complexes from 2‐thiouracil with Cu(II) (6,7) and Pt(II) (8) have been prepared and characterized by spectroscopic methods. All the complexes were assayed for their anti‐HIV‐1 and HIV‐2 activity by examination of their inhibition of HIV‐induced cytopathogenicity in MT‐4 cells. Compound 3 was found to be the most active inhibitor against HIV‐2 in cell culture (EC50 = >18.9 μ g/mL, selectivity index (SI) = 3), which provided a good lead for further optimization. Compounds 6 and 7 exhibited some activity (EC50 = >7.12 μ g/mL and >2.23 μ g/mL) against HIV‐1 and HIV‐2, but no selectivity was observed (SI <1). © 2010 Wiley Periodicals, Inc. Heteroatom Chem 22:44–50, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.20654

Experimental study on the thermochemistry of 2-thiouracil, 5-methyl-2-thiouracil and 6-methyl-2-thiouracil

“…The introduction of a -CH 3 group in the position (6) of the uracil and of the 2-thiouracil ring provides more stabilization than similar introductions in the position (5).…”

“…The chemotherapeutic activity of 2-thiouracil has been explained on the basis of its ready incorporation into the nucleic acid [2]: 2-thiouracil and its derivatives have been found to induce modifications in the thyroid gland, and thus, are known as an antithyroid drugs [3,4]. Thiouracils and a series of derivatives of thiouracils have also found their way into many pharmacological applications for anti-HIV [5,6] and heart diseases treatments [7,8].…”

“…The synthesis, structural studies, and anti-HIV activity of some new complexes of metal ions of 2-thiouracil were recently reported [5].…”

Effect of the sulfur atom on S2 and S4 positions of the uracil ring in different DNA:RNA hybrid microhelixes with three nucleotide base pairs

“…Although the nucleobases with sulfur appear with the same distribution of acceptors and donors groups that the natural nucleobases with oxygen, however, the thiobases cause specific changes in the properties. Thus, a large number of thiouracil derivatives have been used in numerous pharmacological applications, and also attract attention for anti‐HIV, heart diseases treatments, and others . Nucleosides containing 2‐thiouracil are modified units that appear essentials in natural and synthetic nucleic acids .…”

Synthesis and Biological Evaluation of New Dipyridylpteridines, Lumazines, and Related Analogues

“…), the folic acid anti‐metabolite having pteridine nucleus, owe its cytotoxicity by inhibiting the enzyme dihydrofolate reductase and an effective drug for the treatment of breast cancer , leukemia , and lymphoma . The capability of pteridines and pterines for simulating the reactivity of metal sites in several enzymes encouraged many laboratories to synthesize the metal complexes of these molecules . The synthesis of various lumazine nucleosides via multi‐step synthesis was a part of our program to explore such type of compounds .…”