Synthesis and antitumor studies of novel benzopyrano-1,2,3-selenadiazole and spiro[benzopyrano]-1,3,4-thiadiazoline deri
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Med Chem Res DOI 10.1007/s00044-012-0201-0
ORIGINAL RESEARCH
Synthesis and antitumor studies of novel benzopyrano-1,2,3selenadiazole and spiro[benzopyrano]-1,3,4-thiadiazoline derivatives S. I. El-Desoky • F. A. Badria • M. A. Abozeid E. A. Kandeel • A. H. Abdel-Rahman
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Received: 21 April 2012 / Accepted: 9 August 2012 Springer Science+Business Media, LLC 2012
Abstract A convenient and efficient synthetic protocol of new selenadiazole and thiadiazoline derivatives incorporating benzopyranone moiety from readily available starting materials was described. Reaction of different 2,2-dialkyl and 2,2-spirocycloalkyl dihydrobenzopyranones 1a–e with semicarbazide hydrochloride and thiosemicarbazide afforded the corresponding semicarbazones 2a–e and thiosemicarbazones 3a–e, respectively. Furthermore, cyclization of the semicarbazones 2a–e via oxidation using selenium dioxide gave a novel series of chromenoselenadiazoles 4a–e. A series of spirobenzopyrano-1,3,4-thiadidazolines 5a–e were synthesized by refluxing of the thiosemicarbazones 3a–e in acetic anhydride. The synthesized compounds were tested in vitro against four cancer cell lines namely: MCF-7, VERO, WI-38, and HEPG-2. In vivo studies were also performed using Ehrlich ascites carcinoma for antitumor activity. Interestingly, Compounds 4b and 5a showed significant antitumor activities and were capable to improve the hematological parameters as well as increase the mean survival time of the mice bearing tumor.
S. I. El-Desoky (&) M. A. Abozeid E. A. Kandeel A. H. Abdel-Rahman Chemistry Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt e-mail: [email protected] F. A. Badria Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
Keywords Benzopyranone Chromeno-1,2,3-selenadiazole 1,3,4-Thiadiazoline Antitumor activity
Introduction Substituted benzopyran-4-ones are common among natural products and they have been used to prepare various heterocyclic ring systems. On the other hand, the interesting pharmacological activities of selenium heterocycles are well known (Gleiter and Schehlmann, 1990; Lalezari et al., 1974). In addition, selenium is a key component of several major metabolic pathways in human, including thyroid hormone metabolism, antioxidant defense system, and immune function (Chen et al., 2009). Also, selenium supplementation could reduce the incidence of various cancer types such as prostate, lung, colon, and liver cancers (Chen et al., 2009; El-Bayoumy and Sinha, 2004). It is well known that a number of heterocyclic compounds containing nitrogen and sulfur heteroatoms exhibited a wide variety of biological activities (Ellis, 1977; Joshi et al., 2006; Sharma and Sarita, 1994). Moreover, the diazole system is found in numerous antiparasitic, fungicidal, and antiinflammatory drugs (Baht et al., 2005). Some 1,2,3-selena and 1,3,4-(thia)diazoles were found to possess antitumor activity (Klayman and Gunther, 1972; Atta et al., 2010). In view of remarkable pharmacological efficien
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