Novel Insight into Inhibitor Binding of Highly Symmetric HIV‐1 Protease

Abstract

HIV‐1 protease inhibitor binding. Inhibitor binding towards HIV‐1 protease subsites was investigated by the introduction of hydrogen bond acceptor and donor functions into the phenylic substituents of cage dimeric 1,4‐dihydropyridines. Determined affinity constants Ki are discussed and suggested binding modes towards enzyme′s subsites are confirmed by docking studies.

Multidrug resistance reversal properties and cytotoxic evaluation of representatives of a novel class of HIV-1 protease inhibitors

“…Recently we developed structurally‐varied cage dimeric 1,4‐dihydropyridines (H17, JW41, JW33 and JW46; Figure 1) as a novel class of HIV‐1 protease inhibitors with a nonpeptidic molecular scaffold [17] . First, representatives of them were systematically evaluated as P‐gp inhibitors to estimate their potential to effectively work as P‐gp inhibitors in following co‐administered therapies with other HIV‐1 protease inhibitors.…”

“…The synthesis of the compounds H17, JW41, JW33 and JW46 has been described [17] . Verapamil as Isoptin injection solution was purchased from Abbott GmbH & Co. KG (Wiesbaden, Germany).…”

Hantzsch-Like One-Pot Three-Component Synthesis of Heptaazadicyclopenta[a,j]anthracenes: A New Ring System

“…Multicomponent reactions represent an attractive synthetic strategy, as they offer the advantages of simplicity, atom-economy, selectivity, and efficient rapid access to complex organic compounds. [1][2][3][4][5] The Hantzsch reaction is one of the most common multicomponent routes for the synthesis of 1,4-dihydropyridines, which have a broad spectrum of biological and pharmacological activities, including anticancer, 6 antiviral, 7 anticonvulsant, 8 antitubercular, 9 antiinflammatory, 10 anticonvulsant, 11 and anti-Alzheimer activities. 12 In addition, pyrazolo [1,5-a]pyrimidine derivatives exhibit a wide range of bioactivities, that include KDR kinase inhibitory activity, 13 CRF-1 receptor antagonistic activity, 14 antiproliferative activity, 15 and antischistosomal activity.…”

Effects of Structural Symmetry on NMR Spectra of 3,9-Diazatetraasteranes

“…The tetraasterane was synthesized by a dimerization of 1,4cyclohexadiene derivatives, while the 3,9-diazatetraasterane was aza-analogous of tetraasterane and synthesized by a dimerization of 1,4-dihydropyridine derivatives [4][5][6]. With a C 2 symmetric property, the C 2 -3,9-diazatetraasteranes was synthesized via the self-dimerization of the 1,4-dihydropyridines, which exhibited anti-HIV-1 protease activity, anti-tumor activities, modulating multidrug resistance (MDR) towards P-glycoprotein, and other physiological and pharmacological activities [7][8][9][10][11][12]. While non-C 2 -3,9diazatetraasteranes was synthesized via the cross-dimerization of different 1,4-dihydropyridines [13].…”