Halogen Bond Interactions of Novel HIV-1 Protease Inhibitors (PI) (GRL-001-15 and GRL-003-15) with the Flap of Protease Are Critical for Their Potent Activity against Wild-Type HIV-1 and Multi-PI-Resistant Variants | Zendy

Shinichiro Hattori | Zendy; Hironori Hayashi | Zendy; Haydar Bulut | Zendy; Kalapala Venkateswara Rao | Zendy; Prasanth R. Nyalapatla | Zendy; Kazuya Hasegawa | Zendy; Manabu Aoki | Zendy; Arun K. Ghosh | Zendy; Hiroaki Mitsuya | Zendy

Open Access

Halogen Bond Interactions of Novel HIV-1 Protease Inhibitors (PI) (GRL-001-15 and GRL-003-15) with the Flap of Protease Are Critical for Their Potent Activity against Wild-Type HIV-1 and Multi-PI-Resistant Variants

Author(s) -

Shinichiro Hattori,

Hironori Hayashi,

Haydar Bulut,

Kalapala Venkateswara Rao,

Prasanth R. Nyalapatla,

Kazuya Hasegawa,

Manabu Aoki,

Arun K. Ghosh,

Hiroaki Mitsuya

Publication year - 2019

Publication title -

antimicrobial agents and chemotherapy

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.07

H-Index - 259

eISSN - 1070-6283

pISSN - 0066-4804

DOI - 10.1128/aac.02635-18

Subject(s) - darunavir , protease , stereochemistry , chemistry , hiv 1 protease , active site , human immunodeficiency virus (hiv) , enzyme , viral load , antiretroviral therapy , biochemistry , virology , biology

We generated two novel nonpeptidic HIV-1 protease inhibitors (PIs), GRL-001-15 and GRL-003-15, which contain unique crown-like tetrahydropyranofuran (Crn-THF) and P2′-cyclopropyl-aminobenzothiazole (Cp-Abt) moieties as P2 and P2′ ligands, respectively. GRL-001-15 and GRL-003-15 havemeta -monofluorophenyl andpara -monofluorophenyl at the P1 site, respectively, exert highly potent activity against wild-type HIV-1 with 50% effective concentrations (EC50 s) of 57 and 50 pM, respectively, and have favorable cytotoxicity profiles with 50% cytotoxic concentrations (CC50 s) of 38 and 11 μM, respectively.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research