Synthesis of 2-azetidinone derivatives of 6-nitro-1H-indazole and their biological importance

Samadhiya, Pushkal; Sharma, Ritu; Srivastava, Santosh K.; Srivastava, S. D.

doi:10.1590/s0100-40422012000500010

Cited by 13 publications

(6 citation statements)

References 10 publications

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“…12,13 Compounds containing the azetidinone nucleus have been reported to possess diverse pharmacological activities. 14,15,16,17 The indole moiety is present in approved as well as experimen tal drugs and the azetidinone moiety in experimental drugs. 18,19,20 Therefore, in the present investigation, it was envisaged that if these two pharmacophores are linked together this would generate new molecular templates Figure 1, which are likely to exhibit antidepressantlike action in animal models.…”

Section: Introductionmentioning

confidence: 99%

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

Kerzare¹,

Menghani²,

Khedekar³

2018

IJPER

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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.

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Section: Introductionmentioning

confidence: 99%

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

Kerzare¹,

Menghani²,

Khedekar³

2018

IJPER

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“…2 Todavia, após a bedaquilina houve um aumento notável no número de artigos reportando compostos com potente atividade antituberculose. [22][23][24][25][26][27][28] Diversos núcleos heterociclicos e subunidades estruturais já foram relatados como grupamentos farmacofóricos com potente atividade antimicobacteriana, como por exemplo derivados furoxânicos, 27,29 nitroimidazólicos, 30 ftalimídicos, 31 cumarínicos, 32 tiofênicos, 33 fluoroquinolônicos, 34 quinolínicos, 35,36 N-acilhidrazônicos, 37 quinoxalínicos 38 e fluorados. 39 Atualmente, diversos métodos e estratégias são utilizados para o desenvolvimento de novos fármacos contra a TB, como por exemplo: 1) abordagens genéticas para identificação de novos alvos; 2) ensaios de triagem em larga escala utilizando a micobactéria como plataforma; 3) ferramentas de biologia estrutural e triagem virtual e; 4) modificações moleculares em fármacos existentes.…”

Section: (Fase 3) (4) (Figura 1)unclassified

Potenciais alvos moleculares para o desenvolvimento de novos fármacos antituberculose

2017

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POTENTIAL MOLECULAR TARGETS FOR ANTITUBERCULOSIS DRUG DISCOVERY. Tuberculosis (TB) is an infectious disease caused by mycobacteria from the Mycobacterium genus, mainly by Mycobacterium tuberculosis (MTB). The World HealthOrganization (WHO) aims to reduce the number of TB cases worldwide in the coming years. Nevertheless, the increasing number of multidrug-resistant (MDR-TB) and extensive-drug resistance (XDR-TB) strains, and the ineffectiveness of the current treatment in latent tuberculosis are challenges to be overcome. In this review, we will demonstrate the recent advances in the tuberculosis drug discovery, focusing the research of new molecular targets in the Mycobacterium tuberculosis. Among the promising targets described herein, we highlight those, which act in different pathways in the mycobacteria, such as energy metabolism, cell wall biosynthesis, DNA synthesis, iron metabolism and transport through membranes. Furthermore, bioactive compounds discovered using phenotypic assays screening and validated through genetic approaches are also presented.Keywords: medicinal chemistry; tuberculosis; Mycobacterium tuberculosis; molecular targets; new drugs. INTRODUÇÃOA tuberculose (TB) é uma doença infecciosa causada por micobactérias do complexo Mycobacterium, no entanto, a espécie responsável pelo maior número de casos de morbidade e mortalidade é o Mycobacterium tuberculosis (MTB). 1 Ocupando o ranking mundial como a principal causa de mortes causadas por doenças infecciosas, nos últimos anos a tuberculose ultrapassou, em número de casos, a infecção causada pelo vírus da imunodeficiência humana (HIV). 2,3 O último levantamento realizado em 2015 pela Organização Mundial da Saúde (OMS) apontou 9.6 milhões de novos casos no mundo e 1.5 milhões de mortes causadas pela doença. 3 Somado a esses dados, o surgimento e aumento de cepas de M. tuberculosis multirresistente aos fármacos (MDR-TB) e extensivamente resistente aos fármacos (XDR-TB) vêm alarmando as autoridades de todo o mundo. Essas formas de tuberculose apresentam baixas taxas de cura e maiores taxas de mortalidade devido às dificuldades de tratamento. 4 Além disso, já foram relatados na clínica casos de tuberculose totalmente resistente aos fármacos (TDR-TB). 5,6 Ao longo dos últimos anos, é possível constatar algumas evoluções no desenvolvimento de compostos candidatos a fármacos que possam atuar contra a TB. 7 Após um intervalo de mais de 50 anos sem novos medicamentos para o tratamento da TB, a bedaquilina foi aprovada em 2012 pela agência norte-americana U.S. Food and Drug Administration (FDA) para o tratamento de MDR-TB. Atualmente, diversos candidatos a fármacos estão em estudos clínicos, [8][9][10][11][12] 39 Atualmente, diversos métodos e estratégias são utilizados para o desenvolvimento de novos fármacos contra a TB, como por exemplo: 1) abordagens genéticas para identificação de novos alvos; 2) ensaios de triagem em larga escala utilizando a micobactéria como plataforma; 3) ferramentas de biologia estrutural e triagem virtual e; 4) modificações ...

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“…The 2-azetidinone skeleton, otherwise known as the β-lactam ring, has been recognized as a useful building block in the synthesis of biologically important compounds. Azetindin-2-one derivatives display interesting biological activities such as antifungal, antimicrobial [ 1 , 2 , 3 , 4 ], antitubercular [ 5 , 6 ], analgesic, anti-inflammatory [ 7 , 8 ], chymase inhibitory [ 9 ], antitumoral [ 10 , 11 , 12 ], antiviral, antidiabetic and cholesterol absorption inhibitory properties [ 13 ]. The activity of famous antibiotic classes such as the penicillins, cephalosporins, carumonam, aztreonam, thienamicine, nocardicins and carbapenems is attributed to the presence of an 2-azetidinone ring [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of New 2-Azetidinones with Sulfonamide Structures

et al. 2013

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New series of N-(arylidene)hydrazinoacetyl sulfonamides 4a1–6, 4b1–6 and N-(4-aryl-3-chloro-2-oxoazetidin-1-yl)aminoacetyl sulfonamides 5a1–6, 5b1–6 were synthesized. The structures of the new derivatives was confirmed using spectral methods (FT-IR, 1H-NMR, 13C-NMR). The antibacterial activities of these compounds against Gram positive (Staphyloccoccus aureus ATCC 6583, Staphyloccoccus epidermidis ATCC 12228, Enterococcus faecalis ATCC 25912) and Gram negative (Klebsiella pneumoniae CIP 53153, Proteus vulgaris CIP 104989, Citrobacter freundii CIP 5732, Enterobacter cloacae CIP 103475, Escherichia coli ATCC 25922, Pseudomonas aeruginosa CIP 82118) bacterial strains were evaluated using the broth micro-dilution method. Compound 4a2 displayed the highest antibacterial activity, especially against Staphyloccoccus epidermidis, Enterococcus faecalis and Pseudomonas aeruginosa. The antioxidant potential of the synthesized compounds was also investigated according to ferric reducing power, total antioxidant activity and DPPH radical scavenging assays. All tested compounds showed excellent antioxidant activity in comparison with sulfadiazine and sulfisoxazole which were used as parent sulfonamides. Moreover, some of them showed an antioxidant activity comparable with that of ascorbic acid. In general, the compounds designed based on a sulfadiazine skeleton (compounds 4a1–6, 5a1–6) are more active than those obtained from sulfisoxazole (compounds 4b1–6, 5b1–6), and the N-(arylidene)hydrazinoacetyl sulfonamide derivatives 4a1–6, 4b1–6 are more active than their azetidionone analogues 5a1–6, 5b1–6.

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Synthesis of 2-azetidinone derivatives of 6-nitro-1H-indazole and their biological importance

Cited by 13 publications

References 10 publications

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

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

Potenciais alvos moleculares para o desenvolvimento de novos fármacos antituberculose

Synthesis and Biological Evaluation of New 2-Azetidinones with Sulfonamide Structures

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