Synthesis and Pharmacological Evaluation of Bis-Compounds Containing Benzothiazole and Schiff Base

Abstract

Inflammation is the body’s response to injury and danger. It is the central communication network and regulatory process that senses and controls threat, damage, containment, and healing, which are all critical aspects in the maintenance of an organism’s integrity. Chronic inflammation represents a major pathologic basis for the majority of human malignancies. Approximately, 25% of all cancers are somehow associated with chronic infection and inflammation. The role of inflammation in carcinogenesis has been extensively investigated and well documented. Many biochemical processes that are altered during chronic inflammation have been implicated in tumorogenesis. Extensive literature review revealed that compounds containing benzothiazole or schiff base or bis type of structural features have good pharmacological activity. Hence 2- (benzo[d]thiazol-2-ylimino)methyl) benzylidene)benzo[d]thiazol-2-amine derivatives were designed and synthesized which contain all three features. Structural elucidation of the synthesized compounds was done by F.T.I.R, 1H NMR and Mass spectroscopy. Analgesic activity of synthesized compound was carried out by acetic acid induced writhing method and all the compound showed good activity at the same dose compare to standard diclofenac sodium (25mg/kg). Anti-inflammatory activity of compounds was done by rat paw edema method and compound containing fluoro, nitro and bromo substitution at six position showed good activity compared to standard (50 mg/kg). Anticancer activity of compounds were evaluated in vitro on A-375 cell line (Human Malignant Melanoma; Skin), DU-145 cell line (Human; Prostate; Carcinoma), HCT-15 cell line (Human; Colon Adenocarcinoma) by XTT assay method and Doxorubicin taking as a reference standard. In accordance with data obtained from In-vitro activity, both compounds have shown good activity against all three cell lines in different concentrations. But in comparison of individual cell line both compounds show more potent activity compared to standard in A-375. Where as in DU- 145 cell line 6-nitro (102) is equipotent and in HCT-15 cell line 6-fluoro (87) shows more potency than standard. Overall, designed compounds showed better pharmacological activity and can be proved as better candidate for future investigations.