Investigation of nucleoside analogs with anti‐HIV activity

Abstract

ABSTRACT:Although a relatively large number of drugs that inhibit human immunodeficiency syndrome (HIV)-1 reverse transcriptase have been developed-such as AZT, d4T, ddI, 3TC, and ddC, which are chain terminating nucleoside analogs-resistance is still a major problem. Atomic charges, regioselective patterns of chemical reactivity, and other indices of biochemical activity may help us acquire a better understanding of how the drugs work and the mechanism of drug resistance. In this work, we investigated the above-mentioned nucleoside analogs using the ab initio Hartree-Fock method with 3-21G, 3-21G*, 6-31G, 6-31G*, 6-31G**, and 6-31ϩG** basis sets as well as B3LYP/6-31G**, including thus diffusion, polarization, and correlation effects to obtain fully optimized geometric parameters. Vibrational frequencies were calculated and we also investigated the effects of solvents, Mulliken, and natural bond orbital charge distribution, as well as hydrogen bond effects. We tried to correlate very low and very high anti-HIV activity with charges, vibrational stretching frequencies, interatomic distances, and the effect of solvents.

Identification of lamivudine conformers by Raman scattering measurements and quantum chemical calculations

“…The C conformer shows hydrogen bonding interactions between the C O of the pyrimidine ring and two hydrogen atoms, and the D conformer shows three hydrogen bonding interactions involving the oxygen atom of the thymine carbonyl group. Arissawa et al [10] have calculated the vibrational frequencies and have investigated the effects of solvents, Mulliken, and natural bond orbital charge distribution, as well as HB effects in nucleoside analogs with anti-HIV activity such as AZT, d4T, ddl, 3TC, and ddC. They tried to correlate very low and very high anti-HIV activity with charges, vibrational stretching frequencies, interatomic distances, and the effect of solvents.…”

Structure and conformational analysis of the anti-HIV reverse transcriptase inhibitor AZT using MP2 and DFT methods. Differences with the natural nucleoside thymidine. Simulation of the 1st phosphorylation step with ATP

“…For instance, efficient phosphorylation depends largely on the spatial structure of the nucleoside, specially the O5 0 H orientation. 5,8,18,[37][38][39][40] The current manuscript completes our extensive investigation of the conformational families of the 2 0 ,3 0 -didehydro-2 0 ,3 0 -dideoxy analogues of the canonical nucleosides. For this reason, the conformers of natural nucleosides and nucleoside analogues have been analyzed by different authors.…”

Homology modeling and molecular interaction field studies of α-glucosidases as a guide to structure-based design of novel proposed anti-HIV inhibitors

“…The use of computer-aided molecular design has been very useful for investigating diseases, such as AIDS, cancer, allergies, Alzheimer and Chaga's disease [1][2][3][4][5][6][7][8]. AIDS, for example, has been for too long a major challenge to the international scientific community.…”