Please use this identifier to cite or link to this item: https://ir.swu.ac.th/jspui/handle/123456789/27560
ชื่อเรื่อง: Structural Basis of 2-Phenylamino-4-Phenoxyquinoline Derivatives as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors
ผู้แต่ง: Makarasen A.
Patnin S.
Vijitphan P.
Reukngam N.
Khlaychan P.
Kuno M.
Intachote P.
Saimanee B.
Sengsai S.
Techasakul S.
Keywords: protein binding
quinoline
quinoline derivative
RNA directed DNA polymerase
RNA directed DNA polymerase inhibitor
binding site
chemical structure
chemistry
conformation
dose response
drug effect
วันที่เผยแพร่: 2022
บทคัดย่อ: New target molecules, namely, 2-phenylamino-4-phenoxyquinoline derivatives, were designed using a molecular hybridization approach, which was accomplished by fusing the pharmacophore structures of three currently available drugs: nevirapine, efavirenz, and rilpivirine. The discovery of disubstituted quinoline indicated that the pyridinylamino substituent at the 2-position of quinoline plays an important role in its inhibitory activity against HIV-1 RT. The highly potent HIV-1 RT inhibitors, namely, 4-(2′,6′-dimethyl-4′-formylphenoxy)-2-(5″-cyanopyridin-2″ylamino)quinoline (6b) and 4-(2′,6′-dimethyl-4′-cyanophenoxy)-2-(5″-cyanopyridin-2″ylamino)quinoline (6d) exhibited half-maximal inhibitory concentrations (IC50) of 1.93 and 1.22 µM, respectively, which are similar to that of nevirapine (IC50 = 1.05 µM). The molecular docking results for these two compounds showed that both compounds interacted with Lys101, His235, and Pro236 residues through hydrogen bonding and interacted with Tyr188, Trp229, and Tyr318 residues through π–π stacking in HIV-1 RT. Interestingly, 6b was highly cytotoxic against MOLT-3 (acute lymphoblastic leukemia), HeLA (cervical carcinoma), and HL-60 (promyeloblast) cells with IC50 values of 12.7 ± 1.1, 25.7 ± 0.8, and 20.5 ± 2.1 µM, respectively. However, 6b and 6d had very low and no cytotoxicity, respectively, to-ward normal embryonic lung (MRC-5) cells. Therefore, the synthesis and biological evaluation of 2-phenylamino-4-phenoxyquinoline derivatives can serve as an excellent basis for the development of highly effective anti-HIV-1 and anticancer agents in the near future. © 2022 by the authors. Licensee MDPI, Basel, Switzer-land. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
URI: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85122826468&doi=10.3390%2fmolecules27020461&partnerID=40&md5=ef82d4a9faedb24b8054c2983f69c7df
https://ir.swu.ac.th/jspui/handle/123456789/27560
ISSN: 14203049
Appears in Collections:Scopus 2022

Files in This Item:
There are no files associated with this item.


Items in SWU repository are protected by copyright, with all rights reserved, unless otherwise indicated.