title: In vitro antiviral activities of myristic acid analogs against human immunodeficiency and hepatitis B viruses.
abstract: A group of myristic acid analogs, designed as alternative substrates for N-myristoyltransferase (NMT), were evaluated against human immunodeficiency virus (HIV), hepatitis B virus (HBV) and duck hepatitis B virus (DHBV) in vitro. Antiviral potency was increased when S or O was substituted for -CH2- in myristic acid and selectivity was affected by the presence and position of the heteroatoms and phenyl groups. A correlation was established among anti-HIV activity, Log P and Log D7.4 and between anti-HIV activity and carbonyl-heteroatom interatomic distances in the myristoyl analogs. 12-Thioethyldodecanoic acid 6 was moderately active (EC50 = 9.37 microM) against HIV-infected T4-lymphocytes (CEM-SS cell line), and it exhibited in vitro activity (EC50 = 17.8 microM) against HBV-producing 2.2.15 cell cultures derived from a human hepatoblastoma cell line (Hep G2). 12-Methoxydodecanoic acid 1 exhibited in vitro activity (EC50 = 20-30 microM) against hepatitis B in the HBV DNA-transfected 2.2.15 cell line. At a concentration of 10 microg/ml, none of the fatty acids significantly inhibited the replication of DHBV in infected hepatocytes.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Parang
authors.forename: L I
authors.initials: LI
authors.lastname: Wiebe
authors.forename: E E
authors.initials: EE
authors.lastname: Knaus
authors.forename: J S
authors.initials: JS
authors.lastname: Huang
authors.forename: D L
authors.initials: DL
authors.lastname: Tyrrell
authors.forename: F
authors.initials: F
authors.lastname: Csizmadia
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004353:Drug Evaluation, Preclinical; D005227:Fatty Acids / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D015611:Hepatitis B Virus, Duck / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D009227:Myristic Acids / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D005227:Fatty Acids; D009227:Myristic Acids; D013440:Sulfides; D014764:Viral Proteins