Papers by Francisco Cardenas
![Research paper thumbnail of Synthesis and Antitumor Evaluation of New Thiazolo[5,4- b ]quinoline Derivatives](https://a.academia-assets.com/images/blank-paper.jpg)
Journal of Medicinal Chemistry, 1997
A new synthesis of 9-hydroxy- and 9-(alkylamino)thiazolo[5,4-b]quinolines by cyclization of 4-(et... more A new synthesis of 9-hydroxy- and 9-(alkylamino)thiazolo[5,4-b]quinolines by cyclization of 4-(ethoxycarbonyl)-5-(arylamino)thiazoles and 5-(arylamino)-4-carbamoylthiazoles, respectively, is described. In vitro cytotoxicity of a large number of derivatives of these compounds has been tested against several cell lines. The highest activities observed are associated with the presence of a 2-[[(N,N-diethylamino)ethyl]amino] substituent at C-2 and a fluorine atom at the C-7 position of the tricyclic planar heteroaromatic framework. Three structural features seem to be essential for antitumor activities: a positive charge density at carbon C-7, a side chain at position C-2 or C-9 of the thiazoloquinoline skeleton with two basic nitrogens and a pKa value of 7.5-10 in the most basic center, and a conformational flexibility of this basic side chain. These structural requirements must be simultaneously satisfied in order to ensure a significant antitumor activity.
Journal of Organic Chemistry, 2003
Aplidine (dehydrodidemnin B), a natural product with potent antitumor activity currently in multi... more Aplidine (dehydrodidemnin B), a natural product with potent antitumor activity currently in multicenter phase II clinical trials, exists in DMSO as a mixture of four slowly interconverting conformations in a ratio of 47:33:13:7. NMR spectroscopy shows that these arise as a consequence of cis/trans isomerization about the NMe-Leu(7)-Pro(8) and Pro(8)-Pyr amide bonds of the molecule's side chain. Two major conformations account for 47% and 33% of the total population, a ratio of 60:40 between the two. They correspond to the cis- and trans-isomers, respectively, about the Pro(8)-Pyr amide bond. Two minor conformers arise as a consequence of similar isomerism about the Pro(8)-Pyr amide bond, but in structures in which the NMe-Leu(7)-Pro(8) amide bond is cis rather than trans. These account for approximately 13% and 7% of the total population, corresponding to a ratio of 65:35 cis/trans, respectively. Molecular dynamics simulations show that the three-dimensional structures of all four conformational isomers are similar in the macrocycle and that all are essentially unchanged with respect to the macrocycle of didemnin B. Significant differences in the conformation of the molecule's side chain are, however, observed between major and minor pairs. Analysis of hydrogen-bonding patterns shows that each major conformer exhibits a beta-turn like structure and is stabilized by hydrogen bonding between a different carbonyl group of the pyruvyl unit of the molecule's side chain and the NH of the Thr(6) residue. The minor isomers have a cis-amide bond between the NMe-Leu(7) and Pro(8) residues that obliges the side chain to adopt an extended disposition where hydrogen bonding to the macrocycle is absent. These results suggest that the ability of the molecule's side chain to adopt a beta-turn-like conformation may not be a prerequisite for biological activity in the didemnins and that conformations having an extended side-chain may play a role in the biological activity of aplidine.
Journal of Medicinal Chemistry, 2004
With the aim of studying the contribution of the II turn conformation at the side chain of didemn... more With the aim of studying the contribution of the II turn conformation at the side chain of didemnins to the bioactive conformation responsible for their antitumoral activity, conformationally restricted analogues of aplidine and tamandarin A, where the side chain dipeptide Pro 8 -N-Me-D-Leu 7 is replaced with the spirolactam II turn mimetic (5R)-7-[(1R)-1-carbonyl-3-methylbutyl]-6-oxo-1,7-diazaspiro[4.4]nonane, were prepared. Additionally, restricted analogues, where the aplidine (pyruvyl 9 ) or tamandarin A [(S)-Lac 9 ] acyl groups are replaced with the isobutyryl, Boc, and 2-methylacryloyl groups, were also prepared. These structural modifications were detrimental to cytotoxic activity, leading to a decrease of 1-2 orders of magnitude with respect to that exhibited by aplidine and tamandarin A. The conformational analysis of one of these spirolactam aplidine analogues, by NMR and molecular modeling methods, showed that the conformational restriction caused by the spirolactam does not produce significant changes in the overall conformation of aplidine, apart from preferentially stabilizing the trans rotamer at the pyruvyl 9 -spirolactam amide bond, whereas in aplidine both cis and trans rotamers at the pyruvyl 9 -Pro 8 amide bond are more or less equally stabilized. These results seem to indicate a preference for the cis form at that amide bond in the bioactive conformation of aplidine. The significant influence of this cis/trans isomerism upon the cytotoxicity suggests a possible participation of a peptidylprolyl cis/trans isomerase in the mechanism of action of aplidine.
Journal of Organic Chemistry, 2001
Debido a que aun existen con mucha fuerza posiciones reduccionistas en un sentido u otro o sea., ... more Debido a que aun existen con mucha fuerza posiciones reduccionistas en un sentido u otro o sea., de una parte los biologicistas, preformistas o con residuos de preformismo, que no tienen en cuenta el papel de los social y lo cultural como un aspecto decisivo en el proceso de formación del ser humano y su psicología y por otro los ambientalistas, que poco o nada le atribuyen a las condiciones biológicas y en particular a las funciones del cerebro. En este artículo partimos, de una síntesis, o sea que concebimos el cerebro, como aquellos que es, esencialmente, un producto de la evolución biológica que, además, incluye la historia de la cultura y sin él, no se hubiera dado una de las condiciones necesarias para el surgimiento de la psiquis humana, pero la segunda necesaria y suficiente condición fue, el proceso de construcción de la cultura y de la actividad y la comunicación social. Este proceso filogenético se sintetiza en cada generación y es lo que hace que devenga el proceso de formación del ser humano ontogenéticamente.
Cheminform, 2010
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Cheminform, 1992
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Euphytica, 1964
Genetic resistance to race alpha of C. lindemuthianum in the nine varieties of beans studied can ... more Genetic resistance to race alpha of C. lindemuthianum in the nine varieties of beans studied can be accounted for by dominant alleles at either of two loci, which are unlinked and which behave as duplicate factor loci in the classical sense. A similar system of loci governs reaction to races beta and gamma, with evidence favoring multiple allelism and dominance of alleles conferring susceptibility in certain instances in the case of beta. In addition, for reaction to races beta and gamma, there are distinct systems of complementary factors, again with multiple allelism at the beta loci. Finally, there is genetic linkage between genes of the duplicate factor set governing reaction to gamma and genes of the duplicate factor set, and complementary factor set conditioning reaction to beta. The genes that are members of the set(s) pertaining to any one race alone are independent of each other in a linkage sense.
Communications in Algebra, 1993
Diseases of The Colon & Rectum, 1964
El desarrollo histórico de la humanidad trae como consecuencia el desarrollo de la ciencia y la t... more El desarrollo histórico de la humanidad trae como consecuencia el desarrollo de la ciencia y la técnica. Surge la pedagogía como ciencia de la educación; pero no sola, aislada, sino como parte de la sociedad donde se desarrolla y como reflejo de una concepción filosófica y psicológica propia de una clase y una época determinada.
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Papers by Francisco Cardenas