Hit optimization studies of 3-hydroxy-indolin-2-one analogs as potential anti-HIV-1 agents

Abstract

In the current study, twenty-two compounds based upon 3-hydroxy-3-(2-oxo-2-phenylethyl)indolin-2-one nucleus were designed, synthesized and in vitro evaluated for HIV-1 RT inhibition and anti-HIV-1 activity. Compounds 3d, 5c and 5e demonstrated encouraging potency against RT enzyme as well as HIV-1 in low micromolar to nanomolar concentration with good to excellent safety index. Structure activity relationship studies revealed that halogens such as bromo or chloro at 5th the position of oxindole ring remarkably enhanced the potency against RT. Moreover, methoxy or chloro groups at the ortho position of phenyl ring also significantly favored RT inhibition activity. Seven compounds (3b, 3c, 3d, 3e, 5b, 5c and 5e) with better anti-HIV-1 potency were tested against the mutant HIV-1 strain The putative binding mode, as well as interaction patterns of the best active compound 5c with wild HIV-1 RT were studied via docking studies.

New less toxic zeolite‐encapsulated Cu(II) complex nanomaterial for dual applications in biomedical field and wastewater remediation

“…Synthesis and spectroscopic investigation of both chromone‐based and isatin‐based complexes have attracted particular interest as a result of the importance of these compounds and their diverse applications involving anti‐microbial, anti‐oxidant, anti‐viral, anti‐tumor, anti‐HIV and other properties …”

Enantioselective synthesis of 3-hydroxy- and 3-amino-3-alkynyl-2-oxindoles by the dimethylzinc-mediated addition of terminal alkynes to isatins and isatin-derived ketimines

“…Finally, to show the potential of our catalytic system we tested our ligand in the enantioselective synthesis of two pharmacologically active 5,6 compounds, 5a and 5b , derived from N -methylisatin (Scheme 1). Both chiral propargylic alcohols were obtained in a good yield under our optimized reaction conditions.…”

“…1). For example, 3-(hex-1-yn-1-yl)-3-hydroxy-1-methylindolin-2-one ( I ) shows excellent biological activity in Echinococcus multilocularis metacestodes, which can cause severe liver problems, 5 3-(cyclopropylethynyl)-3-hydroxy-1,5-dimethylindolin-2-one ( II ) is more active than efavirenz against HIV-1 replication 6 and 5-chloro-3-ethenyl-3-hydroxy-1-(prop-2-yn-1-yl)indolin-2-one ( III ) is a good inhibitor of the enzyme Akt kinase with potential anticancer activity. 7 In addition, 3-alkynyl-3-hydroxy-2-oxindoles and 3-alkynyl-3-amino-2-oxindoles are commonly used as versatile synthons in a wide variety of synthetic applications, 8 notably the preparation of biologically active spirooxindoles 9 and other heterocyclic derivatives (Fig.…”

Research progress on the antiviral activities of natural products and their derivatives: Structure–activity relationships

“…Substitution with bromine or chlorine at position 5 (R1) of the oxindole ring enhanced its antiviral activity significantly. Compound (40A) with a chlorine substitution had higher antiviral activity (IC 50 = 5.92 μM), whereas little antiviral potency was observed in case of substitution of bromine on the oxindole ring with hydrogen ( Chander et al, 2018 ). Moreover, the antiviral activity varied depending on the type and position of the substituents on the benzene ring.…”