Synthesis and Biological Evaluation of Isatin Based Thiazole Derivatives

Biological Evaluation of Isatin Based Thiazole Derivatives Isatin is an important class of nitrogen containing heterocyclic aromatic compounds, found in plants, human blood and tissue, and considered as very attractive compound in medicinal chemistry. On the other hand, thiazole heterocyclic derivatives are other important key compounds received wide attention in pharmaceutical industry. In this study, we have synthesized series of isatin based thiazloe derivatives, elucidated their structures with different spectroscopic techniques, such as FTIR and Proton nuclear magnetic resonance spectroscopy and screened for Lipoxygenase inhibitory potential.


Introduction
Isatin is an important class of nitrogen containing heterocyclic aromatic compounds, found in plants, human blood and tissue and acts as important specie for the synthesis of various heterocyclic compounds especially, indolic and quinolinic compounds [1]. Isatinbased multicomponent reactions are one of the preferred strategies for the one pot synthesis of spirooxindole fused heterocycles [2].
Isatin (1H-indole-2,3-dione) derivatives show a broad spectrum of biological activities such as antibacterial, antifungal, antiviral, anti-inflammatory, anti-convulsant and anticancer drug [3,4]. Some of the Istin derivatives have been approved for clinical uses. Its derivatives represent an important class of heterocyclic compounds that can be used as precursors for drug synthesis [5]. Due to the importance of this derivative and its wide range of applications, it is justified to apply the "Lord of the Rings" of aromatic compounds.
Therefore, designing attractive new decorative structures remains a positive challenge and a goal of many research groups [6,7].
Isatin moiety is responsible for a wide spectrum of biological property such as anticancer and antiviral in many synthetically versatile molecules [8]. Isatin derived ketimines represent readily available synthetic precursors of the 3-amino-2-oxindole moiety via enantioselective Mannich type reactions [9,10]. Another indolebased moiety with proven anti-proliferative potential via inhibition treatment of gastrointestinal stromal tumors and advanced renal cell carcinoma [11].
Zhang et al. first reported the vinylogous, henry reaction between isatin and 3,5-dialkyl-4-nitroisoxazole, leading to isoxazolesubstituted 3-hydroxy-2-oxindole derivatives, medicinally important compounds [15], also provided the basis for removal of industrial dye wastewater [16,17]. Isatin based hydrazones are a class of compounds that have been largely used as synthons for the synthesis of heterocyclic compounds because of the presence of various reactive centers in the moiety [18]. Isatin derived propargylic alcohols have been extensively used as versatile synthons in organic synthesis as they incorporate both triple bonds and hydroxyl functional groups [19]. A variety of catalytic enantioselective addition reactions to isatin-derived ketimines have been developed, including Strecker reactions, aza-Henry reactions and aza-Friedel-Crafts reactions etc. [20]. Spirooxindoles, the 3-substituted oxindole unit is recognized as an important structural motif that forms the core of numerous heterocyclic compounds and has a wide spectrum of pharmaceutical activity, such as being a gastrin/CCK-B receptor antagonist, a vasopressin receptor antagonist and antimalarial agent [21]. In this study, here we have discussed in detail the synthesis of isatin and their derivatives particularly in medicinal fields, because isatin plays a key effect like ascorbic acid, hydroxyl amino acids, omeprazole, thiol compounds and imidazole etc.; which is helpful for the pathogenesis of gastric ulcer and peptic ulcer. Also discuss antioxidants, which are responsible for converting free radicals into stable substances, especially serious diseases caused by diabetes. We can say, that isatin provides a critical and dynamic role in the pharmaceutical industry.

Materials and Methods
The synthesis of isatin derivatives was carried out in two-step reactions. In first step, thiosemicarbazide (1 mmol) was mixed with isatin in methanol as a solvent in the presence of HCl as a catalyst and refluxed for 5-7 hrs. Reaction completion was checked by thin layer chromatography. After reaction completion the crude mixture was filter and then washes with methanol. The solid ppt of pure products was obtained. In second step, the product obtained in the first step (1 mmol) was mixed with chloro acetic acid, sodium acetate and aromatic aldehydes (1 mmol) in the presence of glacial acetic acid and refluxed for 6-7 hrs. Reaction completion was checked by thin layer chromatography. After reaction completion, the mixture was filter then wash with glacial acetic acid to obtained pure solid products. water, acetone, and n-hexane were used as such without further distillation. All these chemicals were found 98-99.9% pure. The substrate are used different aromatic aldehydes such as (2-Nitro benzaldehyde), (4-Benzyaloxy-3 methoxy benzaldehyde), (4-Nitro benzaldehyde), (Terepthaldehyde), (4-Hydroxy benzaldehyde),

Lipoxygenase Activity
Compounds 77-89 were evaluated for Lipoxygenase inhibitory potential. Neither of the compounds showed any variable degree of Lipoxygenase inhibition. The inhibitory potential of the all synthesized compounds is too much less, that is why the IC50 value is not calculated for the compounds [22] (Table 2).

Compliance with Ethical Standards
Conflict of interest: The authors declare that they have no conflict of interest.

Ethical Approval
This article does not contain any studies with human participants or animals performed by any of the authors.