Synthesis, antitubercular evaluation and molecular docking studies of phthalimide bearing 1,2,3-triazoles

Phatak, Pramod S.; Bakale, Rajubai D.; Dhumal, Sambhaji T.; Dahiwade, Lalita K.; Choudhari, Prafulla B.; Krishna, Vagolu Siva; Sriram, Dharmarajan; Haval, Kishan P.

doi:10.1080/00397911.2019.1614630

Cited by 50 publications

(20 citation statements)

References 33 publications

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“…Thus, we used in silico approaches to predict the pharmacokinetics and the toxicological potential of 101 phthalimide-1,2,3-triazole derivatives, aiming to identify leader compounds against SARS-CoV-2 ( Figure 1 ). These compounds were categorized according to the radicals attached to the 1,2,3-triazole-phthalimide nucleus into groups A-H, as showed in supplementary material ( Tables S1–S8 ): ( A ) derivatives containing benzyl substituents (Tehrani et al, 2019 ); ( B ) derivatives containing phenyl or benzothiazole groups (Da Silva et al, 2019); ( C ) derivatives containing carbohydrate groups and an additional phthalimide (Assis et al, 2012 ); ( D ) compounds with N -phenylacetamides substituents (Phatak et al, 2019 ); ( E ) presence of benzimidazole group between phtalimide-triazole nucleus and three radicals variations (Singh et al, 2020 ); ( F ) thalidomide derivative analogues (Ronnebaum & Luzzio, 2016 ); ( G ) derivatives of phthalimide-benzamide-1,2,3-triazole (Sadat-Ebrahimi et al, 2020 ); and ( H ) derivatives with an additional phthalimide (López-González et al, 2016 ).…”

Section: Resultsmentioning

confidence: 99%

“…; (B) derivatives containing phenyl or benzothiazole groups(Da Silva et al, 2019); (C) derivatives containing carbohydrate groups and an additional phthalimide(Assis et al, 2012); (D) compounds with N-phenylacetamides substituents(Phatak et al, 2019); (E) presence of benzimidazole group between phtalimide-triazole nucleus and three radicals variations(Singh et al, 2020); (F) thalidomide derivative analogues(Ronnebaum & Luzzio, 2016); (G) derivatives of phthalimide-benzamide-1,2,3-triazole(Sadat- Ebrahimi et al, 2020); and (H) derivatives with an additional phthalimide(L opez-Gonz alez et al, 2016).…”

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confidence: 99%

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Identification of 1,2,3-triazole-phthalimide derivatives as potential drugs against COVID-19: a virtual screening, docking and molecular dynamic study

Holanda

Lima

Silva

et al. 2021

Journal of Biomolecular Structure and Dynamics

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In this work we aimed to perform an in silico predictive screening, docking and molecular dynamic study to identify 1,2,3-triazole-phthalimide derivatives as drug candidates against SARS-CoV-2. The in silico prediction of pharmacokinetic and toxicological properties of hundred one 1,2,3-triazole-phtalimide derivatives, obtained from SciFinderV R library, were investigated. Compounds that did not show good gastrointestinal absorption, violated the Lipinski's rules, proved to be positive for the AMES test, and showed to be hepatotoxic or immunotoxic in our ADMET analysis, were filtered out of our study. The hit compounds were further subjected to molecular docking on SARS-CoV-2 target proteins. The ADMET analysis revealed that 43 derivatives violated the Lipinski's rules and 51 other compounds showed to be positive for the toxicity test. Seven 1,2,3-triazole-phthalimide derivatives (A7, A8, B05, E35, E38, E39, and E40) were selected for molecular docking and MFCC-ab initio analysis. The results of molecular docking pointed the derivative E40 as a promising compound interacting with multiple target proteins of SARS-CoV-2. The complex E40-M pro was found to have minimum binding energy of À10.26 kcal/mol and a general energy balance, calculated by the quantum mechanical analysis, of À8.63 eV. MD simulation and MMGBSA calculations confirmed that the derivatives E38 and E40 have high binding energies of À63.47 ± 3 and À63.31 ± 7 kcal/mol against SARS-CoV-2 main protease. In addition, the derivative E40 exhibited excellent interaction values and inhibitory potential against SAR-Cov-2 main protease and viral nucleocapsid proteins, suggesting this derivative as a potent antiviral for the treatment and/or prophylaxis of COVID-19.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Identification of 1,2,3-triazole-phthalimide derivatives as potential drugs against COVID-19: a virtual screening, docking and molecular dynamic study

Holanda

Lima

Silva

et al. 2021

Journal of Biomolecular Structure and Dynamics

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“…[4][5][6] They act by inhibiting the enzyme enoyl-ACP reductase. [7][8][9] Ciprofloxacin is one of the widely used fluoroquinolones that exhibits potent in vitro and in vivo antimycobacterial activity. Fluoroquinolones are also found to be active against di-verse types of bacteria, including Staphylococcus (S.) aureus, S. epidermis, Bacillus (B.)…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Pharmacological Evaluation of Some C<sub>3</sub> Heterocyclic-Substituted Ciprofloxacin Derivatives as Chimeric Antitubercular Agents

Niveditha¹,

Begum²,

Prathibha³

et al. 2020

CHEMICAL & PHARMACEUTICAL BULLETIN

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A series of new C 3 heterocyclic-substituted ciprofloxacin derivatives were prepared from ciprofloxacin acid hydrazide as possible chimeric molecules. They were evaluated for their possible in vitro antibacterial (agar cup/bore diffusion method) and antitubercular (Lowenstein-Jensen (LJ) slant method) activities. The results indicated that all the test compounds are highly effective against all the bacterial strains and have shown excellent anti-tubercular activity against normal, multidrug resistant and extensively drug resistant strains of Mycobacterium tuberculosis. They were found to be more potent antibacterial and antitubercular agents than the standard, ciprofloxacin. The minimum inhibitory concentration (MIC)'s of all the compounds against M. tuberculosis were found to be 0.0625 µg/mL as compared to ciprofloxacin (MIC 2 to > 8 µg/mL). Molecular docking studies were performed by using AUTODOCK 4.2 on the new ciprofloxacin derivatives at the active site of crystal structure of fluoroquinolones target enzyme Mtb DNA gyrase GyrA N-terminal domain (PDB ID: 3ILW) and also on the active site of crystal structure of chosen heterocyclics target enzyme enoyl-acyl carrier protein (ACP) reductase enzyme (PDB ID: 4TZK). Interestingly, almost all the compounds have shown relatively greater binding affinity at both the active sites than ciprofloxacin. Compound 6 exhibited the highest affinity for 3ILW and 4TZK.

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“…Thus, these the two entities on molecular hybridization to form one new single molecule may offer a new lead with potent anti‐tubercular activity. [ 27 ] In extension of our efforts toward the identification of new anti‐tuberculosis agents [ 28 ] herein, we have planned and synthesized a series of new isoniazid clubbed with 1,4‐disubstituted 1,2,3‐triazole conjugates. The newly synthesized conjugates were screened for their in vitro antitubercular and antimicrobial activities.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of isoniazid‐1,2,3‐triazole conjugates: Antitubercular, antimicrobial evaluation and molecular docking study

Badar

Sulakhe

Muluk

et al. 2020

Journal of Heterocyclic Chem

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In the present study, a series of new isoniazid-1,2,3-triazole conjugates (5a-k) was synthesized via click chemistry approach. The newly synthesized compounds were assessed for their in vitro antitubercular and antimicrobial activities. The compound 5g has displayed potent antitubercular activity against Mycobacterium tuberculosis H37Rv (Mtb) with MIC value 1.56 μg/mL. The active compounds were screened for their cytotoxicity profile by MTT assay against RAW 264.7 cell line. The four compounds have shown good in vitro antimicrobial activities against both antibacterial and antifungal pathogens. A molecular docking study was accomplished to identify the probable mode of action of synthesized derivatives. These compounds have shown excellent binding affinity toward Enoyl-acp reductase (INHA) and DNA gyrase.

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Synthesis, antitubercular evaluation and molecular docking studies of phthalimide bearing 1,2,3-triazoles

Cited by 50 publications

References 33 publications

Identification of 1,2,3-triazole-phthalimide derivatives as potential drugs against COVID-19: a virtual screening, docking and molecular dynamic study

Identification of 1,2,3-triazole-phthalimide derivatives as potential drugs against COVID-19: a virtual screening, docking and molecular dynamic study

Design, Synthesis and Pharmacological Evaluation of Some C<sub>3</sub> Heterocyclic-Substituted Ciprofloxacin Derivatives as Chimeric Antitubercular Agents

Synthesis of isoniazid‐1,2,3‐triazole conjugates: Antitubercular, antimicrobial evaluation and molecular docking study

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