title: Synthesis, biological evaluation and molecular docking of calix[4]arene-based β-diketo derivatives as HIV-1 integrase inhibitors.
abstract: In this publication, we design and report the synthesis of calix[4]arene-based β-diketo derivatives as novel HIV-1 integrase (IN) inhibitors. The target compounds were obtained using Claisen condensation, and their structures were characterized by NMR and ESI-MS. Preliminary bioassays showed that calix[4]arene-based β-diketo derivatives inhibit strand transfer (ST) with IC50 values between 5.9 and 21.2 µM. Docking studies revealed the predominant binding modes that were distinct from the binding modes of raltegravir, which suggests a novel binding region in the IN active site. Moreover, these compounds are predicted not to interact with some of the key amino acids (GLN148 and ASN155) implicated in viral resistance. Therefore, this series of compounds can further be investigated for a possible chemotype to circumvent resistance to clinical HIV-1 IN inhibitors.
authors: College of Chemical Engineering, AnHui University of Science & Technology, Huainan, P. R. China.
authors: Zaigang
authors: Z
authors: Luo
authors: Yu
authors: Y
authors: Zhao
authors: Chao
authors: C
authors: Ma
authors: Zhipeng
authors: Z
authors: Li
authors: Xuemei
authors: X
authors: Xu
authors: Liming
authors: L
authors: Hu
authors: Nianyu
authors: N
authors: Huang
authors: Hongqiu
authors: H
authors: He
mesh_terms: D001665:Binding Sites; D047250:Calixarenes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D024882:Drug Resistance, Viral; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D007659:Ketones / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010636:Phenols / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; D007659:Ketones; D010636:Phenols; C121325:calix(4)arene; D047250:Calixarenes; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1
keywords: Calix[4]arene; HIV-1 integrase inhibitors; Molecular docking; Synthesis; β-Diketo derivatives