Synthesis and Evaluation of Aryl Quinolines as HIV-1 Integrase Multimerization Inhibitors

Authors

Nicholas Jentsch, University of Southern MississippiFollow
Alison P. Hart, University of Southern Mississippi
Jared D. Hume, University of Southern MississippiFollow
Jian Sun, University of Southern MississippiFollow
Kaitlin A. McNeely, University of Southern Mississippi
Chiyang Lama, University of Southern Mississippi
Julie A. Pigza, The University of Southern MississippiFollow
Matthew G. Donahue, University of Southern MississippiFollow
Jacques Kessl, University of Southern MississippiFollow

Document Type

Article

Publication Date

9-14-2018

Department

Chemistry and Biochemistry

Abstract

HIV-1 integrase multimerization inhibitors have recently been established as an effective class of antiretroviral agents due to their potent ability to inhibit viral replication. Specifically, quinoline-based inhibitors have been shown to effectively impair HIV-1 replication, highlighting the importance of these heterocyclic scaffolds. Pursuant of our endeavors to further develop a library of quinoline-based candidates, we have implemented a structure–activity relationship study of trisubstituted 4-arylquinoline scaffolds that examined the integrase multimerization properties of substitution patterns at the 4-position of the quinoline. Compounds consisting of substituted phenyl rings, heteroaromatics, or polycyclic moieties were examined utilizing an integrase aberrant multimerization in vitro assay. para-Chloro-4-phenylquinoline 11b and 2,3-benzo[b][1,4]dioxine 15f showed noteworthy EC₅₀ values of 0.10 and 0.08 μM, respectively.

Publication Title

ACS Medicinal Chemistry Letters

Volume

9

Issue

10

First Page

1007

Last Page

1012

Recommended Citation

Jentsch, N., Hart, A. P., Hume, J. D., Sun, J., McNeely, K. A., Lama, C., Pigza, J. A., Donahue, M. G., Kessl, J. (2018). Synthesis and Evaluation of Aryl Quinolines as HIV-1 Integrase Multimerization Inhibitors. ACS Medicinal Chemistry Letters, 9(10), 1007-1012.
Available at: https://aquila.usm.edu/fac_pubs/15544