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Title: Synthesis, Characterization & Biological Evaluation of Benzimidazole Based Novel Heterocyles
Authors: Yousaf, Muhammad
Keywords: Social Sciences
Issue Date: 2020
Publisher: Abdul Wali Khan University, Mardan
Abstract: The aim of this dissertation is to report some of the novel benzimidazole derivatives and to evaluate their biological activities such as anti-oxidant, urease inhibition, alpha-glucosidase, acetyl cholinesterase inhibition, butyryl cholinesterase inhibition, alpha-amylase, carbonic anhydrase and human neutrophil study. This thesis is divided into three chapters and each chapter contains a series of different compounds along with the reported biological activities. Chapter 1 contains synthesis of novel hydrazone derivatives based on 2- Mercaptobenzimidazole. 2-MBI based hydrazone derivatives were carried out through multistep reactions. In first step, 2-Mercaptobenzimidazole was refluxed with bromoethane in basic condition (KOH). After getting shiny white needle like crystals of 2-ethylthio benzimidazole was refluxed with ethyl chloroacetate (drop wise) using anhydrous K2CO3 and the product (2-(2-(ethylthio)benzimidazolyl)acetate) was obtained. In the third step, 2-(2-(ethylthio)benzimidazolyl)acetate was refluxed with hydrazine and the obtained product, 2-((ethylthio)benzimidazolyl)acetohyrazide was precipitated. In the final step, 2-((ethylthio)benzimidazolyl)acetohyrazide was refluxed with different aldehydes and obtained a series of hydrazone derivatives. All these novel hydrazone derivatives (149-182) were evaluated for different biological activities such as acetyl cholinesterase, butyryl cholinesterase alpha-amylase, urease, alpha-glucosidase and human neutrophil study. Most of the compounds showed excellent inhibition against these enzymes. For example, the whole series have shown better inhibition against AChE but compounds 155, 152, 182, 161, 179 and 157 showed good inhibition with excellent docking score. Similarly, compounds 152, 182, 155, 157, 162 and 168 were found to be the most active against butyryl cholinesterase enzyme. The IC50 range of these compounds was between 10 to 21 μg/mL as compared to the standard galantamine with IC50 is 5.21 μg/mL. Human neutrophil activity of these compounds was also very good. Out of 34 compounds, only four compounds were toxic towards human neutrophils. xix The 2nd chapter of this dissertation includes synthesis of 1,3,4-oxadiazole derivatives (117-137) based on 2-MBI. Acylhydrazone derivative was dissolved in 5 mL DMSO proceeded by the addition of potassium carbonate and cyclizing agent i.e. iodine and get 1,3,4-oxadiazole derivatives. All the designed compounds of this series were screened against acetyl cholinesterase enzyme and most of the compounds showed potent inhibition against this enzyme. Compounds 128, 118, 119, 131, 124, 125 etc. showed good inhibitions with IC50 range is in between 15 to 40 μg/mL as compared to the standard galantamine with IC50 is 12.98 μg/mL. The whole series was docked against acetyl cholinesterase and all of them showed better docking score. Similarly, compounds 128, 118, 119, 124, 131, 117 etc. also proved potent inhibitions against butyryl cholinesterase enzyme might be due to the electron donating groups in these compounds. This series also showed safe profile against human neutrophil with low toxicity effects. Alpha-glucosidase inhibition study of 1,3,4-oxadiazole derivatives were also found good. The 3rd chapter describes one of the most important class of heterocyclic compounds i.e. thiazolidinone group. In this chapter we report newly synthesized 4-thiazolidinone derivative (146-176). Acylhydrazone derivative was cyclized into 4-thiazolidinone derivatives using cyclizing agent i.e thioglycolic acid with molten zinc chloride. All the compounds of this series were tested against acetyl cholinesterase enzyme and majority of the compounds enjoyed powerful inhibition. For example compound 172, 148, 150 and 171 showed good inhibition with high ranked docking score. Furthermore, all of these compounds were evaluated for antioxidant activity and most of the compounds showed excellent activity against standard acorbose. Urease studies of these compounds were also found upto high range.
Gov't Doc #: 20557
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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