THERAPEUTIC POTENTIAL OF RO-5-3335 - A NEW ACTIVE BENZODIAZEPINE AGAINST HIV-1 VIRUSES INVITRO, RESISTANT OR NON-RESISTANT TO AZT

Ro 5-3335 is a new benzodiazepine highly active in vitro (IC50 = 0.1 - 1.0 mM) against HIV-1 viruses of AIDS resistant or non-resistant to z idovudine (AZT). It is also active against HIV-2. Ro 5-3335 is origina l by its mechanism of action, acting on the trans-activation factor of transcription (TAT) and non on the reverse transcriptase. Such as, it could prevent proviral DNA to express in both evolutive and silent AI DS resistant or non-resistant to AZT or to other anti-reverse transcri ptase series. In addition, in antagonizing extracellular TAT's actions , Ro 5-3335 could alleviate the syndrome commonly associated with AIDS as Kaposi's syndrome. In rodent test, Ro 5-3335 has no diazepam-like central effects and presents in comparison to AZT a more favorable the rapeutic index. In dog, the elimination half-life, peak concentration and availability are 2 h, 0.8 muM and 85 % respectively, after a 1 mg. kg-1 oral dose of Ro 5-3335. Theoretically, Ro 5-3335 and now its anal ogue Ro 24-7429 seem to possess all vertues to antagonize evolutive an d latent AIDS. Its arrival is timely to cope with the ever increasing resistance phenomena, lengthy development of AIDS vaccines, exponentia l contamination of populations worldwide and last but not least possib ly to impede evolutions of the disease. Ability to manipulate TAT-medi ated activation of HIV-1 genes paves the ways to study conceivable cor rections of abnormal gene expressions of neurotransmitters, hormones, oncogenes and key enzymes.