PMID- 31542957 OWN - NLM STAT- MEDLINE DCOM- 20191216 LR - 20191217 IS - 1029-046X (Electronic) IS - 1026-776X (Linking) VI - 30 IP - 10 DP - 2019 Oct TI - Molecular docking, design, synthesis and biological evaluation of novel 2,3-aryl-thiazolidin-4-ones as potent NNRTIs. PG - 697-714 LID - 10.1080/1062936X.2019.1653364 [doi] AB - Nonnucleoside reverse transcriptase inhibitors (NNRTIs) remain the most promising anti-AIDS agents that target the HIV-1 reverse transcriptase enzyme (RT). However, the efficiency of approved NNRTI drugs has decreased by the appearance of drug-resistant viruses and side effects upon long-term usage. Thus, there is an urgent need for developing new, potent NNRTIs with broad spectrum against HIV-1 virus and with improved properties. In this study, a series of thiazolidinone derivatives was designed based on a butterfly mimicking scaffold consisting of a substituted benzothiazolyl moiety connected with a substituted phenyl ring via a thiazolidinone moiety. The most promising derivatives were selected using molecular docking analysis and PASS prediction program, synthesized and evaluated for HIV-1 RT inhibition. Five out of fifteen tested compounds exhibited good inhibitory action. It was observed that the presence of Cl or CN substituents at the position 6 of the benzothiazole ring in combination with two fluoro atoms at the ortho-positions or a hydrogen acceptor substituent at the 4-position of the phenyl ring are favourable for the HIV RT inhibitory activity. FAU - Geronikaki, A AU - Geronikaki A AD - School of Pharmacy, Aristotle University of Thessaloniki , Thessaloniki , Greece. FAU - Petrou, A AU - Petrou A AD - School of Pharmacy, Aristotle University of Thessaloniki , Thessaloniki , Greece. FAU - Kartsev, V AU - Kartsev V AD - InterBioscreen , Moscow , Russia. FAU - Eleftheriou, P AU - Eleftheriou P AD - Department of Biomedical Sciences, School of Health Sciences, International Hellenic University , Thessaloniki , Greece. FAU - Boga, R AU - Boga R AD - BogaR Laboratories LLC , Suwanee , USA. FAU - Bartolo, B AU - Bartolo B AD - Faculty of Sciences, Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza" IGM-CNR , Pavia , Italy. FAU - Crespan, E AU - Crespan E AD - Faculty of Sciences, Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza" IGM-CNR , Pavia , Italy. FAU - Franco, G AU - Franco G AD - Faculty of Sciences, Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza" IGM-CNR , Pavia , Italy. FAU - Maga, G AU - Maga G AD - Faculty of Sciences, Institute of Molecular Genetics "Luigi Luca Cavalli-Sforza" IGM-CNR , Pavia , Italy. LA - eng PT - Journal Article DEP - 20190923 PL - England TA - SAR QSAR Environ Res JT - SAR and QSAR in environmental research JID - 9440156 RN - 0 (Reverse Transcriptase Inhibitors) RN - EC 2.7.7.- (reverse transcriptase, Human immunodeficiency virus 1) RN - EC 2.7.7.49 (HIV Reverse Transcriptase) SB - IM MH - *Drug Design MH - HIV Reverse Transcriptase/*antagonists & inhibitors MH - HIV-1/*drug effects MH - *Molecular Docking Simulation MH - Reverse Transcriptase Inhibitors/*chemical synthesis/*pharmacology MH - Structure-Activity Relationship OTO - NOTNLM OT - AIDS OT - HIV-1 reverse transcriptase OT - NNRTIs OT - PASS prediction OT - Thiazolidin-4-ones OT - molecular docking EDAT- 2019/09/24 06:00 MHDA- 2019/12/18 06:00 CRDT- 2019/09/24 06:00 PHST- 2019/09/24 06:00 [pubmed] PHST- 2019/12/18 06:00 [medline] PHST- 2019/09/24 06:00 [entrez] AID - 10.1080/1062936X.2019.1653364 [doi] PST - ppublish SO - SAR QSAR Environ Res. 2019 Oct;30(10):697-714. doi: 10.1080/1062936X.2019.1653364. Epub 2019 Sep 23.