Anti-Human Immunodeficiency Virus (HIV) Activity of the Novel Antiviral Antibiotic Quartromicins which Enhance Inhibitory Effect of 3′-azido-2′,3′-dideoxythymidine (AZT) in vitro

Abstract

Novel antiviral antibiotic quartromicins A1 and 01, isolated from Amyco/atopsis orienta/is, significantly inhibited human immunodeficiency virus (HIV)-induced cytopathic effect and virus specific antigen expression at concentrations of 25-100/1g rnl"" in MT-4 cells infected with HTLV-III B • The reverse transcriptase activity of disrupted HTLV-III B particles, recombinant HIV-1 enzyme, and purified avian myeloblastosis virus (AMY) enzyme were also significantly inhibited by quartromicins A1 and 01. The combined antiviral effect of quartromicin A1 and AZT on the replication of HIV in MT-4 cells was also examined. Quartromicin A1 synergistically enhanced the inhibitory effect of AZT as revealed by HIV-specific antigen expression.

Partial Stereochemical Assignment of Quartromicins A3 and D3

“…The quartromicins − are a structurally unique group of metabolites from actinomycetes species with a wide array of biological properties, including activity against several important viral targets including herpes simplex virus (HSV) type 1, influenza, and human immunodeficiency virus (HIV) . Members of the quartromicin family are also known to inhibit phospholipase A 2 (PLA 2 ) .…”

Studies on the Synthesis of Quartromicins A3 and D3: Synthesis of the Vertical and Horizontal Bis-Spirotetronate Fragments

“…α-Hydroxy aldehyde exo-8b was oxidized by exposure to KOH and I 2 in MeOH, 34 and then the primary TBS ether was cleaved by treatment with PPTs in MeOH. The diol exo-16 was acylated by treatment with Ac 2 O and catalytic Sc(OTf) 3, 35 and then the primary acetate was selectively cleaved by treatment with DIBAL-H. The resulting α-acetoxy ester 17 was then elaborated to exo-18 by using our previously published sequence.…”

“…Other spirotetronate natural products that have attracted interest as synthetic targets include okilactomycin, 21, 22 and tetronothiodin. 23 Our synthetic strategy aims to exploit the C 2 symmetry of the natural products by generation of the carbocycle via a late stage dimerization of either the vertical (3) or horizontal (4) exoendo bis-tetronate fragments ( Figure 2). Towards this end, we have developed and report herein syntheses of the "exo-endo" bis-spirotetronate units 3 and 4.…”

Recent advances in the field of bioactive tetronates

“…Tanabe-Tochikura et al demonstrated the anti-HIV activity of quartromicins A 1 and D 1 in vitro (with half-maximum efficient doses of 6.6 and 18.4 mg mL À1 , respectively), which was suggested to be due to inhibition of viral reverse transcription. 140 Tetronothiodin was reported as a highly selective CCK B receptor antagonist. 141 While CCK B receptors are mainly found in brain tissue and have been implicated in anxiety, satiety and nociception, CCK A receptors are located in the gastrointestinal tract.…”