Full Paper Synthesis, Characterization, Antioxidant and Antitumor Evaluation of Some New Thiazolidine and Thiazolidinone Derivatives Moustafa A. Gouda 1 and Ameen A. Abu-Hashem 2 1 Chemistry Department, Faculty of Science, Mansoura University, Mansoura, Egypt 2 Photochemistry Department (Heterocyclic Unit), National Research Center, Dokki, Giza, Egypt 2-(2-Cyano-acetylamino)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid ethyl ester (2) was utilized as a key intermediate for the synthesis of thiocarbamoyl derivative 3 via its reaction with phenyl isothiocyanate. Treatment of 3 with chloroacetyl chloride afforded thiazolidin-5-one 4. Compound 7 reacted with different a-halo carbonyl compounds to give thiazolidine 8a,b, and thiazolidin-4-one derivatives 9. Treatment of 4 with the appropriate aromatic aldehyde and tolyl diazonium chloride afforded the corresponding thiazolidin-5-one derivatives 5a,b and 6, respectively. The thiazolidin-4-one derivative 10 was obtained via the reaction of compound 2 with 2- mercaptoacetic acid. Finally, the thiazoline 11 was obtained via the reaction of compound 2 with phenyl isothiocyanate/sulfur. The title compounds were characterized by elemental analyses and spectral data. The quantum mechanical calculations for some compounds were accomplished and subjected for antioxidant and antitumor studies, whereas, some of them exhibited promising activities. Keywords: Antioxidant and Antitumor Activities / Benzothiophenes / PM3-semi-empirical / Thiazolidinone Received: June 4, 2010; Revised: June 29, 2010; Accepted: July 12, 2010 DOI 10.1002/ardp.201000165 Introduction Isothiocyanates have been used as synthetic intermediates to prepare biologically active heterocyclic compounds [1]. The biological and physiological activities of sulfur containing heterocycles may be attributed to the presence of N-C-S-frag- ment characteristic of thiazoles, thiazolines, and thiazoli- dines [2]. On the other hand, 2-aminothiophene-3- carboxylates possess a broad spectrum of biological effective- ness such as analgesic activity [3]. The corresponding 5-carbox- amido-4-hydroxy-3-(b-D-ribofuranosyl)thiophene-2-carbonic acid derivatives were investigated as virucides and virostatic agents [4]. Furthermore, thieno[2,3-d]pyrimidine derivatives [5], showed interesting biological properties including antihypertensive 6], antiallergenic [7], antitumor [8], antiviral [8], anti-HIV-1 [8], and analgesic [9] activities. In view of the above biological importance and in continuation of our previous work [10–14], we aimed to the synthesis of different heterocyclic compounds from readily obtainable thiocarba- moyl intermediates. We reported herein the synthesis, anti- tumor, antioxidant and quantum mechanical calculations of some thiazoline and thiazolidinone derivatives using the pm3 semi-empirical molecular orbital method. Results and discussion Chemistry The Schemes 1–4 describe the synthesis of the target mol- ecules. The starting 2-(2-cyano-acetylamino)-4,5,6,7-tetrahy- dro-benzo[b]thiophene-3-carboxylic acid ethyl ester (2) was obtained with high yield and purity via cyanoacetylation of ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-car- boxylate (1) [15], with 3-(3,5-dimethyl-1H-pyrazol-1-yl)-3- Correspondence: Moustafa A. Gouda, Moustafa Ahmed Gouda, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt. E-mail: dr_mostafa_chem@yahoo.com Fax: (þ2050)2246781 170 Arch. Pharm. Chem. Life Sci. 2011, 11, 170–177 ß 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim