Journui of ~~le~lar Structure (T&z&em), 286 (1993) 247-258 01661280/93/%06.00 0 1993 - Elsevier Science Publishers B.V. All rights reserved 247 Consolation of anti-AIDS agents: computational studies by the PCILO method Anil Saran*, Rajendra P. Ojha’ Chemical Physics Group, Tata Institute of Fundamental Research, Homi Bhabha Road, Bombay 400 005, India (Received 26 February 1993; accepted 4 May 1993) Abstract Conformational preferences of two anti-AIDS agents, 2’, 3~-did~x~h~idine (ddT) and 2’, 3’-dideoxycytidine (ddC) have been investigated by a computational technique using the quantum chemical PCILO method. Com- putations have been carried out on these anti-AIDS agents having CZ/-endo and C3’-endo sugar puckers as well as, on their respective parent molecules, th~idine (T) and deoxycytidine (dC), The results indicate a remarkable similarity in the conformations of these anti-AIDS agents and their parent nucleosides. The biological significance of this result has been discussed in the Iight of our earlier results on the conformation of azidothymidine (AZT) which is the most widely used anti-AIDS drug, Introduction Computational techniques have been established as invaluable tools in the study of confo~ation of biomaterials such as peptides and proteins, nucleo- tides and nucleic acids, biomembranes, drugs, nucleoside antibiotics, etc. [I-6]. These studies have helped greatly in the understanding of the structure, functions and properties of these biomolecnles and also in the design of new bio- materials in medicine and biology. Acquired immuno deficiency syndrome (AIDS) is a fatal infectious disease and the rapid spread of AIDS has caused worldwide concern. AIDS is caused by a retrovirus known as human immuno- deficiency virus (HIV) [7,8] and efforts are directed towards finding an effective drug against HIV. So far, a~doth~idine (AZT) has unambiguously been demonstrated to be the most effective drug * Corresponding author. ’ Permanent address: Physics Department, Gorakhpur University, Gorakhpur 273 009, India. for clinical use in AIDS patients [9-l2]. However, AZT has caused serious toxicity problems in many AIDS patients because it is toxic to bone marrow which leads to anaemia. It also causes headache, anxiety, confusion and insomnia [ 12,131. There- fore, there is a need for an effective and less toxic drug for AIDS patients. 2’, 3’-dideoxynucleosides which result as a con- sequence of the replacement of 2 I- and 3’-hydroxyl groups by hydrogen atoms have been shown to be active against HIV replication [13-191. These anti-AIDS agents are: 2’, 3 ‘-dideoxyadenosine (ddA), 2’, 3 ‘-dideox~nosine (ddI), 2’, 3 ‘-dideoxy- thymidine (ddT), 2’, 3’-dideoxycytidine (ddC) and 2 ‘, 3 ‘-dideoxyguanosine (ddC). Very recently, we have studied the conformational preferences of two of these anti-AIDS agents namely: ddA and dd1 by the quantum mechanical PCILO method 1201 and compared them to those of our results on AZT [6]. The aim of these studies has been to understand the mode of their biological action. Similar studies have been extended to two other anti-AIDS agents, ddT and ddC and their parent