Busso M, Mian A M, Hahn E F, Resnick L
Department of Dermatology, Mount Sinai Medical Center, Miami Beach, FL 33140.
AIDS Res Hum Retroviruses. 1988 Dec;4(6):449-55. doi: 10.1089/aid.1988.4.449.
A series of nucleotide homo- and heterodimers [3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-di-deoxy-5' adenylic acid (AZT-P-ddA), 3'-azido-3'-deoxythymidilyl-(5',5')-2', 3'-dideoxy;-5'-adenylic acid, 2-cyanoethyl ester [AZT-P(CyE)-ddA], 3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-dideoxy-5'-inosinic acid (AZT-P-ddI), and 3'-azido-3'-deoxythymidilyl-(5',5')-3'-azido-3'-deoxy-5'-thymid ilic acid (AZT-P-AZT)] were synthesized and compared with respect to their anti-HIV and cytotoxic properties to their component monomers in vitro. MT-2 cells were infected with HIV (TM) followed by the addition of drug. The dimers and their respective monomers inhibited HIV-induced syncytia formation, reverse transcriptase production, and the expression of HIV p24 antigen. However, on an equimolar basis, greater anti-HIV potency and enhanced cytotherapeutic indices were observed with the heterodimers when compared with their monomers. Nucleotide dimers, such as AZT-P-ddA, should be actively considered for further evaluation as anti-HIV agents.
合成了一系列核苷酸同二聚体和异二聚体[3'-叠氮基-3'-脱氧胸苷酰基-(5',5')-2',3'-二脱氧-5'-腺苷酸(AZT-P-ddA)、3'-叠氮基-3'-脱氧胸苷酰基-(5',5')-2',3'-二脱氧-5'-腺苷酸2-氰基乙酯[AZT-P(CyE)-ddA]、3'-叠氮基-3'-脱氧胸苷酰基-(5',5')-2',3'-二脱氧-5'-肌苷酸(AZT-P-ddI)以及3'-叠氮基-3'-脱氧胸苷酰基-(5',5')-3'-叠氮基-3'-脱氧-5'-胸苷酸(AZT-P-AZT)]，并在体外就其抗HIV和细胞毒性特性与其组成单体进行了比较。用HIV(TM)感染MT-2细胞，随后加入药物。这些二聚体及其各自的单体抑制了HIV诱导的合胞体形成、逆转录酶产生以及HIV p24抗原的表达。然而，在等摩尔基础上，与单体相比，异二聚体表现出更高的抗HIV效力和增强的细胞治疗指数。核苷酸二聚体，如AZT-P-ddA，应积极考虑作为抗HIV药物作进一步评估。
