Determination of perindopril erbumine by oxidative coupling reaction using 2, 6-dichloroquinone-4-chlorimide

Abstract Perindopril erbumine (Perindopril tert-butylamine salt) is a potent angiotensin-converting enzyme (ACE) inhibitor. It is used to treat the patients with hypertension and heart failure problems. A sensitive, inexpensive and precise analytical technique has been developed for the estimation of perindopril in bulk and formulations. The procedure involves the development of colour by forming an oxidative coupling reaction between drug (PPE) and reagent such as 2, 6-dichloroquinone-4-chlorimide (DCQC). The formed colored species were measured at (max=520 nm. The developed method showed linearity within the concentration limits of 25-75 µg mL-1. The linear correlation coefficient (r) and molar absorptivity were found to be 0.9999 and 3.285 x 103 mol-1cm-1. % Recovery ± SD values were in the range of 99.69 - 100.51 (+ 0.42 - ( 0.41) (n=3) which indicates the accuracy of the developed method. The interference of other excipients that are commonly present in formulations is found to be negligible. Precision and accuracy of the proposed method were confirmed by student t-test and F-tests at 95% confidence limits with (n-1) degrees of freedom. The validity parameters of proposed method were calculated by ICH guidelines

Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae) displayed in vitro antileishmanial activity

The therapeutic arsenal for the treatment of Leishmaniasis is limited and includes toxic compounds (antimonials, amphotericin B, pentamidine and miltefosine). Given these aspects, the search for new compounds based on floristic biodiversity is crucial. In the present work, we report the isolation, characterization and antileishmanial activity of six related neolignans (1­6) of bioactive extract from Nectandra leucantha (Lauraceae) twigs. Methods: Dried and powdered twigs of N. leucantha were exhaustively extracted using n-hexane. The crude extract was dereplicated by HPLC/HRESIMS and subjected to column chromatography to yield pure compounds 1­6. Their chemical structures were identified via NMR and comparison of obtained data with those previously published in the literature. Biological assays of compounds 1­6 and their respective monomers (eugenol and methyleugenol) were performed using promastigote and amastigote forms of Leishmania (L.) infantum. Results: Dereplication procedures followed by chemical characterization of isolated compounds by NMR enabled the identification of related neolignans 1­6. Neolignans 2, 4 and 6 showed potential against amastigote forms of L. (L.) infantum (EC50 values of 57.9, 67.7 and 13.7 µM, respectively), while compounds 1 and 3 were inactive. As neolignans 2­4 are chemically related, it may be suggested that the presence of the methoxyl group at C4 constitutes an important structural aspect to increase antileishmanial potential against amastigote forms. Compound 6, which consists of a methylated derivative of compound 5 (inactive) showed antileishmanial activity similar to that of the standard drug miltefosine (EC50 =16.9 µM) but with reduced toxicity (SI = 14.6 and 7.2, respectively). Finally, two related monomers, eugenol and methyleugenol, were also tested and did not display activity, suggesting that the formation of dimeric compounds by oxidative coupling is crucial for antiparasitic activity of dimeric compounds 2, 4 and 6. Conclusion: This study highlights compound 6 against L. (L.) infantum amastigotes as a scaffold for future design of new compounds for drug treatment of visceral leishmaniasis.(AU)

Synthesis and antiproliferative evaluation of new isomeric ellipticine quinones / Síntesis y evaluación de la actividad antiproliferativa de nuevas elipticinquinonas isomericas

The synthesis of new isomeric ellipticine quinones 3a-c and their in vitro antiproliferative activities on cancer cell lines is reported. The designed N-heterocyclic quinones 3a-c were synthesized through a three step sequence which involves: a) one-pot preparation of 4-methoxycarbonyl-3,4-dimethylisoquinoline-5,8-quinone 1 from 2,5-dihydroxyacetophenone, methyl aminocrotonate and silver (II) oxide; b) regioselective amination of 1 with arylamines to give aminoquinones 2a-c and c) palladium-catalyzed intramolecular oxidative coupling of 7-aminoisoquinoline-5,8-quinones 2a-c. The in vitro antiproliferative activity of the new angular quinones was evaluated againts one normal cell line (lung fibroblasts) and gastric, lung and bladder cancer cell lines in 72-h drug exposure assays. The new compounds displayed similar or higher antiproliferative activity with respect to their quinone precursors 2a-c. The isomeric ellipticine quinone 2b appears as the more active member on bladder cancer cell line (IC50: 2.4 uM), comparable to etoposide used as anticancer reference drug...

Se describe la síntesis de las nuevas quinonas 3a-c, isoméricas de elipticina, y sus actividades antiproliferativas in vitro en líneas de células de cáncer. Las quinonas N-heterocíclicas 3a-c se sintetizaron a través de una secuencia que involucra: a) preparación de 4- metoxicarbonil-3,4-dimetlisoquinolin-5,8-quinone 1 a partir de 2,5-dihidroxiacetofenona, aminocrotonato de metilo y óxido de plata (I); b) aminación regioselectiva de 1 con arilaminas para producir las aminoquinonas 2a-c y c) acoplamiento oxidante intramolecular de 7- aminoisoquinolin-5,8-quinonas 2a-c catalizado con paladio. La actividad antiproliferative in vitro de los nuevos compuestos fue evaluada en una línea celular normal (fibroblastos de pulmón) y líneas de células de cáncer gástrico, pulmón y vejiga en ensayos de exposición de 72 horas a la droga. Las quinonas 3a-c exhiben interesantes propiedades antiproliferativas destacando la elipticinquinona isomérica 2b en células de cáncer de vejiga (IC50: 2.4 uM) comparado con etopósido usada como droga anticancer de referencia. Los nuevos compuestos mostraron actividades antiproliferativa similar o mayor respecto de las correspondientes quinonas precursoras 2a-c. La elipticin quinona isomérica 2b corresponde al miembro más activo en células de câncer de vejiga (IC50: 2.4 uM), comparable a la del etopósido, usada como droga anticáncer de referencia...