Pre‐clinical pharmacological profile of QF‐036, a potent HIV‐1 maturation inhibitor

Abstract

Progress in the global therapeutic response to HIV/AIDS has occurred due to the availability of distinct classes of antiretroviral drugs and the advent of highly active antiretroviral therapy. 1-3 However, current therapy is restricted by toxicity and eventual drug resistance. 4 Other factors, such as drug interactions and poor patient compliance, make the effect of treatment less than ideal. Thus, new therapeutic agents with novel targets other than the viral enzymes reverse transcriptase and protease are needed as alternative therapies for those patients who do not respond to approved antiretroviral drugs or cannot tolerate them. 5 HIV assembly and budding have long been a focus of drug development efforts. HIV-1 assembly is driven largely by the Gag precursor protein Pr55 Gag. In coordination with the release of virus particles from the cell surface by budding, the

Selected Plant Triterpenoids and Their Derivatives as Antiviral Agents

“…Among additional phosphate and phosphonate derivatives of bevirimat (24b-24h), compound 24e showed antiviral activity comparable with that of 24a, however, with a slightly worse therapeutic profile than displayed by 24a. A novel compound 25 (Figure 6), in principle, also derived from bevirimat (3), bearing a pyrazolone system in the molecule, has been considered to represent a HIV-1 maturation inhibitor of the third generation [51]. It displayed a maturation inhibition effect in HIV-1 with the EC 50 = 20.36 ± 2.85 nM [51].…”

“…A novel compound 25 (Figure 6), in principle, also derived from bevirimat (3), bearing a pyrazolone system in the molecule, has been considered to represent a HIV-1 maturation inhibitor of the third generation [51]. It displayed a maturation inhibition effect in HIV-1 with the EC 50 = 20.36 ± 2.85 nM [51]. The mechanism of action of 25 is identical to that of the first-generation antiviral maturation inhibitor bevirimat (3).…”

“…The mechanism of action of 25 is identical to that of the first-generation antiviral maturation inhibitor bevirimat (3). However, the investigation showed that 25 displayed better antiviral potential than bevirimat (3) among the virus strains tested, regardless of the presence or absence of human serum [51]. Further designing and developing of suitable molecules resulted in a synthesis of a compound bearing selected, often called "privileged", structural motifs (Figure 6) [52].…”

Acankoreagenin and acankoreosides, a family of lupane triterpenoids with anti‐inflammatory properties: an overview

“…Compound 6e (Cpd 6e) is a potent anticancer agent 26 . Bevirimat (PubChem CID: 457928) is an HIV‐1 maturation inhibitor 12,13 …”

“…This compound, bearing a 3‐ O ‐3′,3′‐dimethylsuccinyl side chain, has been tested in HIV‐1–infected patients but was not effective. However, newer analogs, such as the C‐28 ester derivative EP‐39, α‐keto amides, and a few other BA derivatives, look promising as anti‐HIV‐1 compounds 7,11–13 …”