Isatin thiazoline hybrids as dual inhibitors of HIV-1 reverse transcriptase

Abstract

A series of 3-3-{2-[2-3-methyl-4-phenyl-2,3-dihydro-1,3-thiazol-2-ylidene]hydrazin-1-ylidene-2,3-dihydro-1H-indol-2-one derivatives has been designed and synthesized to study their activity on both HIV-1 (Human Immunodeficiency Virus type 1) RT (Reverse Transcriptase) associated functions. These derivatives are analogs of previously reported series whose biological activity and mode of action have been investigated. In this work we investigated the influence of the introduction of a methyl group in the position 3 of the dihydrothiazole ring and of a chlorine atom in the position 5 of the isatin nucleus. The new synthesized compounds are active towards both DNA polymerase and ribonuclease H in the µM range. The nature of the aromatic group in the position 4 of the thiazole was relevant in determining the biological activity.

N-Propargylamines: versatile building blocks in the construction of thiazole cores

“…Compounds containing these rings have widespread biological applications as anticancer [51–53], anti-HIV [54–55], anti-inflammatory [56], antimicrobial [57–59], and specially antibiotic [60–64] agents. Despite their great relevance in drug design, only very few synthetic methods towards these compounds have been reported to date [44].…”

Hirshfeld analysis and molecular docking with the RDR enzyme of 2-(5-chloro-2-oxoindolin-3-ylidene)-N-methylhydrazinecarbothioamide

“…For example, 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene]amino]thiourea is an in vitro and in silico ISSN 2056-9890 Chikungunya virus inhibitor (Mishra et al, 2016). The title compound (I), 5-chloroisatin-4-methylthiosemicarbazone, is an intermediate in the synthetic pathway of HIV-1 (human immunodeficiency virus type 1) RT (reverse transcriptase) inhibitor synthesis (Meleddu et al, 2017); a new crystal structure determination is reported here, the original work having been published by Qasem Ali et al (2012). Thus, the crystal structure determination of isatin-thiosemicarbazonebased molecules is an intensive research area in medicinal chemistry and the main focus of our work.…”

Crystal structure and Hirshfeld analysis of trans-bis(5-fluoroindoline-2,3-dione 3-oximato-κ2 O 2,N 3)-trans-bis(pyridine-κN)copper(II)

“…From the early years, the chemistry of isatin-based molecules emerged from the synthetic approach to a large class of organic compounds with applications in biochemistry and pharmacology. For two recent examples, see: 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene]amino]thiourea, a derivative with in silico and in vitro inhibition of Chikungunya virus replication (Mishra et al, 2016) and 5-chloroisatin-4-methylthiosemicarbazone, another derivative which appears as an intermediate in the synthesis of an HIV-1 RT inhibitor (Meleddu et al, 2017). The abbreviation HIV-1 RT stands for human immunodeficiency virus type 1 reverse transcriptase.…”