Inhibitory effect of 4‐(2,6‐dichlorophenyl)‐1,2,5‐thiadiazol‐3‐yl‐N‐methyl, N‐ethylcarbamate on replication of human immunodeficiency virus type 1 and the mechanism of action

Abstract

SummaryIn the search for effective antiviral agents, we have found 4-(2, 6-dichlorophenyl)-l, 2, 5-thiadiazol-3-yl-N-methyi, N-ethylcarbamate (RD4-2025) to be a highly potent and selective inhibitor of human immunodeficiency virus type 1 (HIV-1) in vitro. The 50% effective concentration of RD4-2025 for HIV-l-induced cytopathic effect in MT-4 cells was 37 nM, yet no antiviral activity was observed against HIV-2. In HIV-1 reverse transcriptase (RT) assays, RD4-2025 inhibited both RNA-dependent and DNAdependent DNA polymerase activities of a recombinant HIV-1 RT with 50% inhibitory concentrations of 0.11 and 3.5 laM, respectively. However, the compound did not affect the activity of human DNA polymerase ft. Kinetic studies revealed that the inhibition was noncompetitive with respect to dGTP as the substrate and poly(C)/(dG)12.1s as the template/primer. These results were in accordance with those of nonnucleoside RT inhibitors (NNRTIs), such as R89439 (an tx-anilinophenylacetamide derivative) and nevirapine, indicating that RIM-2025 also belongs to the family of NNRTIs.

Valence Electronic Structure of Benzo-2,1,3-chalcogenadiazoles Studied by Photoelectron Spectroscopy and Density Functional Theory

“…There is a long-standing interest in the study of molecules that contain organic heterocycles of nitrogen and one of the chalcogens (sulfur, selenium, or tellurium) due to their many actual and proposed applications, in addition to their sometimes unusual chemistry. In the case of the 1,2,5-chalcogenadiazole ring, the sulfur derivatives can be used in antibacterial and antiviral – agents, insecticides, fungicides, specialized polymers, – and organic LEDs; ,– the corresponding selenium compounds are also applicable as antibacterials, fungicides, , and insecticides ,, in addition to dyes. – All three benzo-2,1,3-chalcogenadiazoles have been investigated as building blocks in supramolecular design because of their propensity to associate through secondary bonding interactions. – …”

Characterization of Human Immunodeficiency Virus Type 1 Strains Resistant to the Non-Nucleoside Reverse Transcriptase Inhibitor RD4–2217

“…We have previously reported the thiadiazole derivatives as novel HIV-1-specific RT inhibitors (Fujiwara et al, 1997;Ijichi et al, 1995). Studies of the mechanism of action have revealed that the thiadiazole derivatives belong to the family of NNRTIs (Ijichi et al, 1996). In this report, we evaluated the genotypic and phenotypic changes of RD4-2217-resistant strains.…”

“…Studies of the mechanism of action have revealed that the thiadiazole derivatives belong to the family of NNRTIs (Ijichi et al, 1996). In this report, we evaluated the genotypic and phenotypic changes of RD4-2217-resistant strains.…”

Direct DNA and PNA probe binding to telomeric regions without classical in situ hybridization

“…This is achieved by exposing the chromosomes to a concentrated solution of formamide at high temperatures, 70 to 80°C, for a few minutes, followed by the addition of the probe which is then allowed to hybridize for multiple hours at 37°C in a formamide solution. Formamide is a useful denaturant as it lowers both the stability and melting point of DNA linearly as the concentration of formamide increases [4]. This hybridization period has been recently shortened to only a few minutes with the use of a microwave; however, the use of formamide in the staining solution was still used [5].…”