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Abstract

Substituted Schiff bases of 1-amino-3-hydroxyguanidine (SB-HAG) were tested for the first time against noninfected T4 lymphocytes (CEM-6 cells) and the same cell line infected by HIV-1 in vitro. Twenty-one of 23 compounds at micromolar levels did not inhibit the growth of the noninfected T4 cells, suggesting minimal cytotoxicity. The antiviral effects of these compounds in a micromolar concentration range have been shown to be nonsignificant (less than 30%) against HIV-1. Three-dimensional parameter focusing of the physicochemical properties (i.e., log P and VW) and the marginal antiviral activities shows that the marginally active compounds lie in a region different from the inactive compounds. QSAR analysis of the two subsets shows that the cytotoxicity correlates well with the electronic and lipophilic parameters. The results of the QSAR analysis can serve as guidelines for further structural modification of this series of compounds to minimize the cytotoxicity against host cells.

Synthesis, Biological Evaluation, and Quantitative Structure−Activity Relationship Analysis of New Schiff Bases of Hydroxysemicarbazide as Potential Antitumor Agents

“…To compare the title compounds with other compounds currently being explored, − further in vivo activity and toxicity studies are needed to assess the potentials of these new compounds as cancer chemotherapeutic agents. The results obtained from this study can be used as guidelines for further improvement of RR inhibitors as anticancer agents.…”

“…Several different classes of compounds such as hydroxyguanidine, thiosemicarbazone, and substituted benzohydroxamic acid and their derivatives have been shown to be RR inhibitors by Lien's group, − Sartorelli's group, , and others. ,− Submicromolar median inhibitory concentrations (IC 50 ) have been observed against various tumor cell lines and viruses for several compounds. Some of the active compounds have shown in vivo anticancer activities and clinical potential. , On the basis of previous studies, an essential pharmacophore [−C(X)NHOH; X = O, NH] has been identified for antitumor/antiviral activities. , …”