Plant growth inhibitory activity of N, N´-di-(4-R-phenyl)-alkanediamides / Actividad inhibitoria de crecimiento de plantas de N, N’-di-(4-R-phenyl)-alcanodiamidas

Diamides are a class of metabolites that occurring in some Meliaceae plants, in Aglaia spp for example, with an ample body of biological activities, being insecticidal and herbicidal two of the most important. In our program of search for botanical pesticides, a series of N,N´-di-(4-R-phenyl)-alkanediamides was evaluated for its herbicidal activity. Many of the analogues tested exhibited moderate to good herbicidal activity both pre-emergence and post-emergence and have been found to inhibit energetic metabolism of pre-emergence weeds. The structure-activity relationships were probed by substitution on the benzene ring. Among the variations investigated, it was found that maximal herbicidal activity was obtained by substitution of –F, -CN and -Br at the aromatic portion and by n=2 of the aliphatic long chain. This last number of carbons (n=2) substitution was the key for the inhibitory activity.

Diamidas son una clase de metabolitos que estan presentes en plantas perteneciente a la familia de la Meliaceas, en Aglaia por ejemplo, poseen un amplio cuerpo de actividades biologicas, siendo la insecticida y la herbicida dos de las mas importantes. En nuestro programa para la busqueda de pesticidas botanicos, una serie de N,N’-di-(4-R-phenyl)-alkanodiamidas se evaluo para su actividad herbicida. Muchos de los analogos exhibieron desde buenas a moderadas actividades, tanto como pre-emergentes como post-emergentes y ademas se encontro que inhiben el metabolismo pre-emergente energetico de malezas. La relacion estructura-actividad fue probada por sustitución sobre al anillo aromatico. Entre las variaciones investigadas, se encontro que la maxima actividad herbicida se obtuvo por sustitución de F, CN y Br en la porcion aromatica y por n=2 del largo de la cadena alifatica. Este ultimo numero de carbonos de sustitución (n=2) fue clave para la actividad inhibitoria.

Tetrahydropyrrolo[3,2-c]azepin-4-ones as a new class of cytotoxic compounds.

Pyrroloazepinones 8a-j and 9a-j were designed by structural modification of lead compound 3. These compounds were tested on five tumor cell lines to determine the role of the azeto ring and the 2-methyl substituent in the cytotoxicity of compound 3. Our results show that compounds 8a-j (R1=CH3) have dramatically reduced cytotoxicity, resulting from the loss of the azeto moiety of lead compound 3. By contrast, azepinones 9a-j (R1=4-nitrophenyl) inhibited the proliferation of almost all cancer cell lines tested even though they lack the azeto ring. Preliminary SAR studies with these compounds revealed the importance of halogens at the para- or meta-position of the 1-phenyl moiety. Additionally, derivatives 9a (R2=H), 9e (R2=4-F), and 9g (R2=4-OMe) were selectively cytotoxic to U-251 cells. However, none of the pyrroloazepinones inhibited the enzymatic activity of CDK1/cyclin B, CDK5/p25, and GSK-3.