Design, Synthesis, Structure−Activity Relationships, and Molecular Modeling Studies of 2,3-Diaryl-1,3-thiazolidin-4-ones as Potent Anti-HIV Agents

Abstract

Starting from 1H,3H-thiazolo[3,4-a]benzimidazoles (TBZs), we performed the design, synthesis, and the structure-activity relationship studies of a series of 2,3-diaryl-1,3-thiazolidin-4-ones. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations with minimal cytotoxicity, thereby acting as nonnucleoside HIV-1 RT inhibitors (NNRTIs). Computational studies were used to delineate the ligand-RT interactions and to probe the binding of the ligands to HIV-1 RT.

Comparative Study of Various Non-Nucleoside Reverse Transcriptase Inhibitors on Different Reverse Transcriptase Enzyme

“…4-Thiazolidone derivatives have attracted continuing interest over the years because of their diverse biological activities including anti HIV activity. [3][4][5][6][7][8][9] these derivatives acts on HIV-1 reverse transcriptase (HIV-1 RT) enzyme. RT inhibitors are of two types: nucleoside reverse transcriptase inhibitors (NRTIs), which act as chain terminators to block the elongation of the HIV-1 viral DNA strand, and non-nucleoside reverse transcriptase inhibitors (NNRTIs), which directly inhibit RT enzyme by binding to the allosteric site near the polymerase active site.…”

Synthesis and Antimicrobial Activities of Some Novel 2,3-Substituted-1,3-Thiazolidin-4-ones Derived from 2-Amino-1,3-thiazole

“…It needs to be accounted to show different physiological activities. They found uses as antitubercular [3], antimicrobial [4][5][6][7][8], antiinflammatory [9], anticancer [10], antihistamines [11], anticonvulsant [12] and as antiviral agents especially as anti-HIV agents [11,13,14]. It has been extensively reported that the antibacterial activity strongly depended on the nature of substituents at C2 and N3 of thiazolidinone ring.…”

Synthesis, characterization and screening of antimicrobial, antituberculosis, antiviral and anticancer activity of novel 1,3-thiazolidine-4-ones derived from 1-[2-(benzoylamino)-4-(methylthio)butyryl]-4-alkyl/arylalkyl thiosemicarbazides

“…7,8 NNRTIs bind in a noncompetetive way to a unique region on the enzyme, namely nonsubstrate-binding site, resulting in alteration of its function and therefore achieving supression of HIV-1 replication with high selectivity. 9 Although combined use of nucleoside inhibitors of RT (NRTIs), non-nucleoside RT inhibitors (NNRTIs) and protease inhibitors (PIs) in the treatment of HIV infections may provide a dramatic recovery in most HIV-infected persons, resistance to the currently used agents remains as a clinical problem. 5 Consequenlty, there is still a need for novel and safe antiviral agents with potent and selective action which are also effective against mutant strains of HIV.…”