Insilico, Synthesis, Characterization and Biological Evaluation of Novel Isatin Analogues

Kaniga, P (2017) Insilico, Synthesis, Characterization and Biological Evaluation of Novel Isatin Analogues. Masters thesis, Arulmigu Kalasalingam College of Pharmacy, Krishnankoil.


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INTRODUCTION:The branch of science concerned with the substance of which matter is composed, the investigation of their properties and reactions, and the use of such reactions to form new substances are called as chemistry. Chemistry is the central science because it bridges other natural sciences, including physics, geology and biology. The atom is the basic unit of chemistry. It consists of a dense core called atomic nucleus surrounded by a space called the electron cloud. The nucleus is made up of positively charged protons and uncharged neutrons, while the electron cloud consists of negatively charged electrons which orbit the nucleus. In a neutral atom, the negatively charged electrons balance out the positive charge of the protons. A chemical element is a pure substance which is composed of a single type of atom, characterized by its particular number of protons in the nuclei of its atoms, known as atomic number and represented by the symbol Z. The mass number is the sum of the number of protons and neutrons in a nucleus. Although all the nuclei of all atoms belonging to one element will have the same atomic number, they may not necessarily have the same mass number, atoms of an element which have different mass number are known as isotops. A pure chemical substance composed of more than one element is called as compound.RESEARCH OBJECTIVES:Nitogen atom containing analogues possess significant pharmacological activities. Various hetero cyclic nucleuses containing nitrogen as a hetero atom such as Indole, Imidazole, Benztriazole, Benzoxazole, Triazole, Tetrazole, and Benzimidazole possess varied pharmacological activities. Imidazole moiety is a versatile lead molecule. It is nitrogen containing heterocyclic ring which possess wide range of biological activities such as anti-bacterial, anti-cancer, anti-tubular, anti-fungal, analgesic and anti-HIV activities. Among, the various synthetic products, the first choice of selection of nucleus in our current research work are isatin. Isatin nucleus have attracted the attention of medicinal chemists due to their wide range of biological activities like as anti-microbial, anti-cancer, anti-convulsant activity and acts as a anxiogenic, sedative and potent antagonist on atrial natriuretic peptide receptors in In-vitro. Isatin derivatives reported exhibit interesting pharmacological activities. The work was planned to perform that isatin was substituted by benzylamine at C-3 position to produce Benzylimino-isatin. The Benzylimino-isatin was substituted by various secondary amines at N-1 position to produce Benzylimino-isatin Mannich bases, exhibits interesting pharmacological activities. The present study is aimed to carry out the synthesis of Benzyliminoisatin Mannich base derivatives. For newer derivatives, Benzylimino-isatin as lead molecule by combining several secondary amines followed by formaldehyde will be synthesized as per literature method. Then, structures will be assigned by FT-IR and 1H NMR analysis. Further, the compounds are evaluated for biological activities such as anti-cancer and anti-microbial activities. In this aim, our current research work was initiated.SUMMARY AND CONCLUSION:Our current research work deals with manually designed, library of compounds (IM1-20) bearing benzylimino-isatin scaffold that performed docking study with E.coli Quinol-Fumarate Reductase with Bound Inhibitor HQNO enzyme (1kf6) [PDB code 1kf6] using Molegro Virtual Docker Evaluation version (MVD 2013.6.0) the best compounds were selected based on their Moldock score in order to synthesis of benzylimino-isatin (IS1)([(3Z)- 3-(benzylimino)-1,3-dihydro-2H-indol-2-one)]) and benzylimino-isatin mannich base derivatives with isatin as a parent moiety. Benzylimino-isatin (IS1) ([(3Z)- 3-(benzylimino)-1,3-dihydro-2H-indol-2-one)]) and benzylimino-isatin mannich bases such as IM1 [(3Z)-3-(benzylimino)-1-[(dimethylamino) methyl]-1, 3- dihydro-2H-indol-2-one], IM3 [(3Z)-3-(benzylimino)-1-[(diphenylamino) methyl]-1, 3-dihydro-2H-indol-2-one], IM4 [(3Z)-3-(benzylimino)-1-[(piperazin- 1-yl methyl)-1, 3-dihydro-2H-indol-2-one], IM5 [(3Z)-3-(benzylimino)-1-[(4- methylpiperazin-1-yl) methyl]-1,3-dihydro-2H-indol-2-one], IM19 [(3Z)-3- (benzylimino)-1-[(morpholin-4-yl methyl)-1,3-dihydro-2H-indol-2-one] & IM20 [2-{[(3Z)-3-(benzylimino)2-oxo-2,3-dihydro-1H-indol-1yl)methyl]}-1H-isoindole- 1,3(2H)-dione] were synthesized by the suitable experimental procedure. The synthesized compounds were characterized by melting point, solubility and subjected to various common analytical techniques like TLC, FT-IR and 1H NMR and it is confirmed by means of their FT-IR and 1H NMR spectrum reports were in complete agreement with the chemical structure. The synthesized compounds were screened for in-vitro anti-microbial activity by disc diffusion method as well as well diffusion method and in-vitro anti-cancer activity by MTT assay method. Among the evaluated compound, three compounds such as IM3 [(3Z)-3-(benzylimino)-1-[(diphenylamino) methyl]-1, 3-dihydro-2H-indol-2-one], IM4 [(3Z)-3-(benzylimino)-1-[(piperazin- 1-yl methyl)-1, 3-dihydro-2H-indol-2-one] & IM20 [2-{[(3Z)-3-(benzylimino)2- oxo-2,3-dihydro-1H-indol-1yl)methyl]}-1H-isoindole-1,3(2H)-dione] have good in-vitro anti-microbial activity at a dose of 50 and 100 μg/0.1 mL, when compared to standard drug Ciprofloxacin at a dose of 10 μg/0.1 mL.Among the evaluated compounds, two compounds such as IM3 [(3Z)-3-(benzylimino)- 1-[(diphenylamino) methyl]-1, 3-dihydro-2H-indol-2-one] & IM20 2-{[(3Z)-3- (benzylimino)2-oxo-2,3-dihydro-1H-indol-1yl)methyl]}-1H-isoindole-1,3(2H)- dione have good in-vitro anti-cancer activity with IC50 0.392 μg/mL and 0.327 μg/mL aagainst human cervical cancer cell line (HeLa cell line) when compared to standard about 5FU with IC50 0.21 μg/mL. From the above facts it can be suggested that the benzylimino-isatin mannich base derivatives finds an interesting field of research because of their varied pharmacological activities.

Item Type: Thesis (Masters)
Additional Information: Reg. No:261515352
Uncontrolled Keywords: Insilico; Synthesis ; Characterization ; Biological Evaluation ; Novel Isatin Analogues
Subjects: PHARMACY > Pharmaceutical Chemistry
Depositing User: Ravindran C
Date Deposited: 16 Mar 2018 09:36
Last Modified: 16 Mar 2018 09:36

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