benzothiazole rings

Abstract This study includes the synthesis of new benzothiazole derivatives that were expected to have biological activity as anticancer agents This study contains four chapters; the first one is an introduction which consists of a brief survey about the different methods used for the synthesis of 2-substituted benzothiazoles and an account on their anticancer activity. The second chapter deals with the aim of the work and schemes that had been carried out to obtain the new required benzothiazole, thiazolidinone, urea, thiourea, amine, bis-benzothiazole and phenol derivatives. The third chapter clarifies the theoretical discussion of the experimental work for the preparation of the starting materials Ia-b, VI and the target compounds IVa-i - XVIa-c. In Scheme 1, the reaction of Ia-b with chloroacetyl chloride afforded the key intermediates IIa-b which upon cyclization with ammonium thiocyanate yielded thiazolidinones IIIa-b. As an extension, reaction of IIIa-b with different aryl and heteroaryl aldehydes afforded IVa-i. In addition, compound IIb was cyclized to give the unexpected compound V instead of nucleophillic substitution when reacted with different substituted anilines. In Scheme 2, the reaction of VI with different aldehydes afforded the Schiff's compounds VIIa-e which upon cyclization with thioglycolic acid yielded thiazolidinones VIIIa-e. Also in Scheme 3, the formation of urea and thiourea derivatives was constructed by reacting VI with 4-chlorophenylisocyanate and ethylisothiocyanate to obtain IX and X respectively. In addition, compound X was cyclized to give thiazolidinone XI using monochloroacetic acid through nucleophillic substitution reaction. Also the reaction of VI with chloroacetyl chloride gave compound XII from which XIIIa-c were obtained via nucleophillic substitution with different primary and/or secondary amines. Furthermore, cyclization of compound XII with ammonium thiocyanate yielded thiazolidinone XIV. Formation of bis-benzothiazole XV was achieved via reacting IV with potassium thiocyanate in presence of bromine as a catalyst. Also the phenolic derivatives XVIa-c were formed via coupling of diazonium salt of VI with different phenols. The structure elucidation of the new compounds was supported by elemental analysis, IR, 1H NMR, 13C NMR in addition to mass spectra. Additionally, a brief account on the docking study was explained through the binding conformation in comparison with the cytotoxic activity. Also, a brief account on the cytotoxic activity was explained. The fourth chapter consists of the experimental part of this work which contains the detailed procedures used for the synthesis of the starting materials Ia-b and VI, the intermediates IIa-b, IIIa-b and XIII the target final compounds IVa-i, V, VIIa-e, VIIIa-e, IX, X, XI, XIIIa-c, XIV, XV and XVIa-c. In addition, data obtained from the element and spectral analyses as well as their physical properties are given in this chapter. It also sheds the light on the anticancer activity in experiment 1, twenty-four compounds of newly synthesized derivatives compared with 2-(4-aminophenyl)benzothiazole (19) as a standard cytotoxic agent against (MCF-7) cell line. Compound XVIc exhibited the highest cytotoxic activity with IC50 12.47 μ M, while in experiment 2, seven compounds of newly synthesized derivatives compared with 2-(4-aminophenyl)benzothiazole (19) as a standard cytotoxic agent against (MCF-7) and (A549) cell lines. Compound IVc exhibited the highest cytotoxic activity with IC50 13.25 μ M and 12.08 μ M against (MCF-7) and (A549) cell lines respectively. This chapter also clarifies the correlation between the results of molecular docking and the anticancer activity.