Synthesis, Characterization, Antidepressant Activity and Docking Studies of Some Novel Indole Bearing Azetidinone Derivatives

Abstract

Context: In general, indole bearing azetidinone derivatives are exhibiting various biological activities. The evaluation of pharmacological potential of the indole bearing azetidinone derivatives as antidepressant agent has been relatively less explored. To get insight of the intermolecular interactions, the molecular docking studies are performed at active site of MAO-A enzyme. Aim: In this study, an attempt has been made to generate new molecular template by linking two pharmacophores (indole and azetidinone), which are likely to exhibit antidepressant-like action in animal models. Methods: The derivatives was synthesized by conventional reactions and characterized by various spectrometric methods. The derivatives were evaluated for antidepressant activity by using forced swim test. Molecular docking studies of the synthesized derivatives with MAO-A enzyme were carried on Vlife MDS Molecular Modelling software, version 4.3.1. by using k-nearest neighbour genetic algorithm method. Results: All the final structures were assigned on the basis of IR, 1 H NMR, mass spectra and elemental analyses. The antidepressant evaluation exhibited final derivatives 26 and 36 as promising molecules with percentage decrease in immobility duration 66.82 and 65.61 respectively. Molecular docking studies are also in agreement with pharmacological evaluation with potent compounds exhibiting dock score -2.8474. Conclusion: It can be concluded that these compounds may have enough potential to be developed as antidepressant agent. It can be further studied for their structure-activity relationship (SAR) studies and developed into potential lead molecules. So our research can make a great impact on those medicinal chemists who work on the development of MAO-A inhibitors.

Conventional and Microwave Synthesis of some new pyridine derivatives and evaluation their antimicrobial and cytotoxic activities.

“…We have synthesized new hybrid compounds containing both entities through the reaction of the obtained imino derivative 7 with chloroacetyl chloride and phenacyl bromide to give compounds 8 and 9, respectively. This is in accordance with previous publication [20] (Scheme 3).…”

New Benzopyrrole Derivatives: Synthesis and Appraisal of Their Potential as Antimicrobial Agents

“…From the starting material isatin, compound 2 was synthesized in high yield using the approach reported by Hassan M. et al (Indole-2,3-dione). Compound 2 was condensed with different substituted aromatic aldehydes to get a Schiff base (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) in the solvent 100 % ethanol. The preparation of pharmacophore, 3-[3chloro-2-substituted-4-oxoazetidin-1-yl]imino-1,3-dihydro-2H-indol-2-one, a pharmacophore was assisted by action of various substituted Schiff bases with chloroacetyl chloride in the presence of triethylamine (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42).…”

“…The benzopyrrole scaffold and its analog can be found in a variety of marine and natural plants [4] . The wide range of chemotherapeutic potential of benzopyrrole is very interesting as a lead in the designing of novel agents, effective against microorganisms, [5,6] cancer, [7] convulsion, [8] inflammation, [9,10] depression, [11] HIV, [12] and other bacteria, benzopyrrole, and its derivatives have garnered a lot of attention in recent decades. Furthermore, the various congeners of azetidinone derivatives were found to have antibacterial and antifungal properties [13–17] …”

“…Thus, the importance of benzopyrrole and azetidinone derivatives in chemotherapeutics prompted us to integrate these two moieties to yield a new lead structure to explore research in antibacterial and antifungal medicines. Thus, in relevant to title of article, synthesis of a series of twenty derivatives of 3-[(substituted benzylidene) hydrazinylidene] 1,3dihydro-2H-indol-2-one (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) and 3 (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) were carried out. The synthesized compounds were explored for both antibacterial as well as antifungal properties.…”

Development of novel indole‐linked pyrazoles as anticonvulsant agents: A molecular hybridization approach

“…[ 36 ] The available scientific literature is abundant with reports on the development of indole‐based molecules against convulsion shown in Figure 1. [ 37–43 ] However, pyrazoles have proved to be a useful structural motif in medicinal chemistry, having applications in the development of drugs for the treatment of cancer, tuberculosis, inflammation, and so forth. [ 44–46 ] Some studies also prove that 1,3,5‐triphenyl‐2‐pyrazoline derivatives possess antidepressant and anticonvulsant activities.…”