IN-VITRO ANTIVIRAL ACTIVITIES OF MYRISTIC ACID ANALOGS AGAINST HUMAN IMMUNODEFICIENCY AND HEPATITIS-B VIRUSES

A group of myristic acid analogs, designed as alternative substrates f or N-myristoyltransferase (NMT), were evaluated against human immunode ficiency virus (HIV), hepatitis B virus (HBV) and duck hepatitis B vir us (DHBV) in vitro. Antiviral potency was increased when S or O was su bstituted for -CH2- in myristic acid and selectivity was affected by t he presence and position of the heteroatoms and phenyl groups. A corre lation was established among anti-HIV activity, Log P and Log D-7.4 an d between anti-HIV activity and carbonyl-heteroatom interatomic distan ces in the myristoyl analogs. 12-Thioethyldodecanoic acid 6 was modera tely active (EC50 = 9.37 mu M) against HIV-infected T4-lymphocytes (CE M-SS cell line), and it exhibited in vitro activity (EC50 = 17.8 mu M) against HBV-producing 2.2.15 cell cultures derived from a human hepat oblastoma cell line (Hep G2). 12-Methoxydodecanoic acid 1 exhibited in vitro activity (EC50 = 20-30 mu M) against hepatitis B in the HBV DNA -transfected 2.2.15 cell line. At a concentration of 10 mu g/ml, none of the fatty acids significantly inhibited the replication of DHBV in infected hepatocytes. (C) 1997 Elsevier Science B.V.