Novel Hydrazones of Isatin Linked N-Phenylacetamides and 1,3,4- Oxadiazoles for Bioappraisal; Synthesis and Characterization

Abstract

Isatin scaffold has been reported to exhibit different pharmacological and biological properties sllch as anti-cancerl - 2 , anti-neuroprotective, anti-diabetic3 - 4. The amide group attached at N-position of isatin scaffold was found to increase the activity against MCF7 cancer cell lines5 . Different hydrazones have also been repOlied as potential agents to treat multiple diseasesG 1o . Due to these properties of isatin, N-phenylacetamides and hydrazones, these are used for the synthesis of lead compound for drug discovety. Similarly, the compounds containing oxadiazole moiety are a part of various marketed drugs. Considering the biological imp0l1ance of all these moieties, in this dissertation isatin hybrids were planned to be synthesized. In part one (a) synthesis of target molecules i.e., hydrazones of isatin-linked N-phenylacetamides (HSI-HS63) and in pati (b) tosyl hydrazones of isatin-linked N-phenylacetamide (NHI-NH7) was carried out. While in part two of this project, hydrazones of oxadiazoles (SH l-SH6) were synthesized successfully. The hydrazones (HSI-HS63) were synthesized from two precursors: N-(N-phenylacetamides)isatin (ASI-AS7) and 2-phenoxyacetohydrazides (PHI-PH9). The precursors (ASI-AS7) were synthesized by the N-acylation of substituted anilines with chloroacetyl chloride which provided 2-chloro-N phenylacetamides (AAI-AA 7) in good to excellent yield, that further reacted with isatin to yield (ASI-AS7). The other precursors (PHI-PH9) were synthesized by the 0- alkylation of phenols with ethyl bromoacetate into ethyl-2-phenoxyacetates (PEl PEIO), followed by the reaction with hydrazine hydrate to form 2- phenoxyacetohydrazides (PHI-PH9). The tosyl hydrazones (NHI-NH7) were synthesized from the reaction of (ASI-AS7) and 4-methylbenzenesulfonohydrazide (TH) (fonned by the reaction of 4-methylbenzenesulfonyl chloride (TS) with hydrazine hydrate). In part two, hydrazones of oxadiazoles (SHl-SH6) were synthesized via condensation reaction of two precursors: isatin-tethered 1,3,4-oxadiazoles (IPLl IPL6) and 2-phenoxyacetohydrazides (PHI-PH6). The ring-closure reaction of (PHl PH6) with carbon disulfide produced oxadiazoles (PLI-PL6) that fwther substituted with 1-(2-bromoethyl)isatin (SI) to provide the precursors (IPLI-IPL6). All the synthesized compounds were characterized by using physical parameters, spectToscopic techniques (FTIR, NMR, LC-MS). The synthesized compounds have the potential to become future drug candidates, hence will be screened for anti-cancer and other biological activities.