Three platinum-chloroquine complexes, trans-Pt(CQDP)2(I)2 [1], trans-Pt(CQDP)2(Cl)2 [2] and trans-Pt(CQ)2(Cl)2 [3], were prepared and their most probable structure was established through a combination of spectroscopic analysis and density functional theory (DFT) calculations. Their interaction with DNA was studied and their activity against 6 tumor cell lines was evaluated. Compounds 1 and 2 interact with DNA primarily through electrostatic contacts and hydrogen bonding, with a minor contribution of a covalent interaction, while compound 3 binds to DNA predominantly in a covalent fashion, with weaker secondary electrostatic interactions and possibly hydrogen bonding, this complex also exerted greater cytotoxic activity against the tumor cell lines.

There are estimated to be more than 20,000 species of plants in Venezuela, of which more than 1500 are used for medicinal purposes by indigenous and local communities. Only a relatively small proportion of these have been evaluated in terms of their potential as antitumor agents. In this study, we screened 308 extracts from 102 species for cytostatic and cytotoxic activity against a panel of six tumor cell lines using a 24-h sulphorhodamine B assay. Extracts from Clavija lancifolia, Hamelia patens, Piper san-vicentense, Physalis cordata, Jacaranda copaia, Heliotropium indicum, and Annona squamosa were the most cytotoxic, whereas other extracts from Calotropis gigantea, Hyptis dilatata, Chromolaena odorata, Siparuna guianensis, Jacaranda obtusifolia, Tapirira guianensis, Xylopia aromatica, Protium heptaphyllum, and Piper arboreum showed the greatest cytostatic activity. These results confirm previous reports on the cytotoxic activities of the above-mentioned plants as well as prompting further studies on others such as C. lancifolia and H. dilatata that have not been so extensively studied.

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Pepsinogen and HCl secretion in the amphibian stomach are performed by a single cell type, the oxyntopeptic cell. These functions were studied in gastric mucosae of toads (Bufo marinus) mounted in Ussing-type chambers. HCl and peptic activity of luminal fluid were measured by titration and proteolysis of albumin, respectively. Distribution of pepsinogen in the gastric mucosa was heterogeneous, activity being highest in the proximal part of the stomach. Zymogen granules in the oxyntopeptic cell were more abundant in the deeper cells of the glands and in the fundus. On stimulation, the granules were released into the lumen of the glands by exocytosis. Histamine, forskolin, or carbachol alone each induced an increase in HCl and pepsinogen secretion. Carbachol after maximal histamine or forskolin stimulation produced an extra increase in both secretions that was greater for pepsinogen response. Similarly, joint addition of carbachol and histamine was more potent than histamine alone for both parameters; however, the effect was greater on pepsinogen release. Pretreatment with cimetidine blocked HCl and pepsinogen responses to carbachol but did not affect responses to forskolin. Addition of omeprazole to forskolin-stimulated mucosae uncoupled the two secretions, inducing a total inhibition of HCl secretion with a slight reduction in pepsinogen secretion. Thus pepsinogen release, similar to HCl secretion, is sensitive to cAMP and Ca(2+)-dependent secretagogues. However, the action of Ca2+ would require the previous elevation of cAMP induced by the different secretagogues. In such a case, the increase in intracellular Ca2+ would result in a nonparallel activation of the two secretions.

Two new gold(I) -chloroquine complexes, Au(CQ)(Cl) (<strong>1</strong>) and Au(CQ)(tgta) (<strong>2</strong>), were prepared and their most probable structure were established through a combination of different spectroscopic and analytical techniques. Their interaction with two important targets of action, DNA and thioredoxin reductase (TrxR), were nvestigated. These studies showed that complexes <strong>1</strong> and <strong>2</strong> displayed two types of interaction with DNA, covalent binding through the metal center, and additionally a non-covalent interaction that is electrostatic in the case of complex <strong>1</strong>, but intercalative for complex <strong>2</strong>, which is similar to that displayed by free CQ. The experimental data indicated that these gold-CQ complexes also possess the ability to inhibit TrxR. These results led us to test their cytotoxicity against 6 tumor cell lines. The complexes displayed cytotoxic activity against the PC-3, SKBR-3, HT-29, LoVo and B16/BL6 lines. These finding suggest that gold(I)-CQ compounds, particularly [Au(CQ)(PPh₃)]PF₆, are promising chemotherapeutic alternatives in the search of anticancer agents.