Anti-AIDS agents 86. Synthesis and anti-HIV evaluation of 2′,3′-seco-3′-nor DCP and DCK analogues

Abstract

In a continuing study of novel anti-HIV agents with drug-like structures and properties, 30 1′-O-, 1′-S-, 4′-O- and 4′-substituted-2′,3′-seco-3′-nor DCP and DCK analogues (8–37) were designed and synthesized. All newly synthesized seco-compounds were screened against HIV-1NL4-3 and a multiple reverse transcriptase (RT) inhibitor-resistant (RTMDR) strain in the TZM-bl cell line, using seco-DCK (7) and 2-ethyl-DCP (4) as controls. Several compounds (14, 18, 19, 22–24, and 32) exhibited potent anti-HIV activity with EC50 values ranging from 0.93 to 1.93 μM and therapeutic index (TI) values ranging from 20 to 39. 1′-O-Isopropoxy-2′,3′-seco-3′-nor-DCP (12) showed the greatest potency among the newly synthesized compounds with EC50 values of 0.47 and 0.88 μM, and TI of 96 and 51, respectively, against HIV-1NL4-3 and RTMDR strains. The seco-compounds exhibited better chemical stability in acidic conditions compared with DCP and DCK compounds. Overall, the results suggested that seco-DCP analogues with simplified structures may be more favorable for development as novel anti-HIV candidates.

Chromone: A Valid Scaffold in Medicinal Chemistry

“…2.24 B, were also proposed as an interesting scaffold for the development of anti-hepatitis C virus drugs [183] . The chromone moiety was also proposed as a putative scaffold for the development of NCEs against the human immunodeficiency virus (HIV), mainly due to their capacity to inhibit the reverse transcriptase [184][185][186] and integrasemediated strand transfer [187] enzymes.…”

RETRACTED ARTICLE: A new synthetic derivative of cryptotanshinone KYZ3 as STAT3 inhibitor for triple-negative breast cancer therapy

“…Natural products are the treasure for drug development, which have been providing novel skeletons and biological compounds to develop new drugs 36 – 38 . Nearly 60% drugs in the market are directly or indirectly derived from natural compounds 39 .…”

Application of Mannich bases to the synthesis of hydroxymethylated isoflavonoids as potential antineoplastic agents

“…Reported routes to C-8 substituted isoflavonoids 3b focused on the hydrolysis of 8-bromomethyl analogs, 17 but these starting materials were not readily available in an efficient process. As a consequence, we required a synthetic route to either C-6 or C-8 substituted 7-hydroxyisoflavonoids 3 (Figure 1), and we employed a proliferation assay using a prostate cancer PC-3 cell line for probing structure-activity (SAR) relationships.…”