Design, Synthesis, Antimicrobial Evaluation, and Molecular Modeling Studies of Novel Indolinedione–Coumarin Molecular Hybrids

Bhagat, Kavita; Bhagat, Jyoti; Gupta, Maneesh K.; Singh, Jatinder; Gulati, Harmandeep Kaur; Singh, Atamjit; Kaur, Kamalpreet; Kaur, Gurinder; Sharma, Shally; Rana, Abhineet; Singh, Harbinder; Sharma, Sahil; Bedi, Preet Mohinder Singh

doi:10.1021/acsomega.8b02481

Cited by 89 publications

(59 citation statements)

References 40 publications

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“…Besides the abovementioned coumarin hybrids, coumarin–pyridine hybrids, [ 116–118 ] coumarin–imine hybrids, [ 119–122 ] coumarin–peptide hybrids, [ 123 ] coumarin–indole hybrids, [ 124 ] coumarin–sulfonamide hybrids, [ 125 ] coumarin–ferrocene hybrids, [ 126 ] coumarin–thiazine hybrids, [ 127 ] coumarin–sugar hybrids, [ 128 ] coumarin–pyran hybrids, [ 129 ] and coumarin–glyoxal hybrids [ 130 ] also showed certain antibacterial activity, but the majority of them were far less potent than the reference drugs. Hence, the enriched SAR may pave the way for further rational design of the novel coumarin hybrids.…”

Section: Miscellaneous Coumarin Hybridsmentioning

confidence: 99%

Coumarin‐containing hybrids and their antibacterial activities

Feng

Zhang

Yang

et al. 2020

Archiv der Pharmazie

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Infections caused by Gram-positive and -negative bacteria are one of the foremost causes of morbidity and mortality globally. Antibiotics are the mainstay of therapy for bacterial infections, but the emergence and wide spread of drug-resistant pathogens have already become a huge issue for public healthcare systems. The coumarin moiety, which is ubiquitous in nature, could bind to the B subunit of DNA gyrase in bacteria and inhibit DNA supercoiling by blocking the ATPase activity; hence, coumarin derivatives possess potential antibacterial activity. Several coumarin-containing hybrids such as coumermycin A1, clorobiocin, and novobiocin have already been used in clinical practice for the treatment of various bacterial infections; thus, it is conceivable that hybridization of the coumarin moiety with other antibacterial pharmacophores may provide opportunities for the development of novel antibiotics. This review outlines the advances in coumarin-containing hybrids with antibacterial potential in the recent 5 years and the structure-activity relationships are also discussed. K E Y W O R D S antibacterial, coumarin, hybrid compounds, structure-activity relationships

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Section: Miscellaneous Coumarin Hybridsmentioning

confidence: 99%

Coumarin‐containing hybrids and their antibacterial activities

Feng

Zhang

Yang

et al. 2020

Archiv der Pharmazie

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“…and S. aureus . [ 40 ] The SAR also demonstrated that the short alkyl linker between the isatin and 1,2,3‐triazole motifs and the introduction of halogen atoms at the C‐5 position of indole moiety were favorable to the antibacterial activity, and the mechanistic study proved that hybrid 8b could act on the active site of S. aureus dihydrofolate reductase.…”

Section: Indole/isatin–coumarin Hybridsmentioning

confidence: 99%

Indole/isatin‐containing hybrids as potential antibacterial agents

Song

Bian

et al. 2020

Archiv der Pharmazie

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The emergence and worldwide spread of drug-resistant bacteria have already posed a serious threat to human life, creating the urgent need to develop potent and novel antibacterial drug candidates with high efficacy. Indole and isatin (indole-2,3-dione) present a wide structural and mechanistic diversity, so their derivatives possess various pharmacological properties and occupy a salient place in the development of new drugs. Indole/isatin-containing hybrids, which demonstrate a promising activity against a panel of clinically important Gram-positive and Gram-negative bacteria, are privileged scaffolds for the discovery of novel antibacterial candidates. This review, covering articles published between January 2015 and May 2020, focuses on the development and structure-activity relationship (SAR) of indole/isatincontaining hybrids with potential application for fighting bacterial infections, to facilitate further rational design of novel drug candidates.

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“…Coumarin is a versatile scaffold having number of applications in medicinal studies like anti‐inflammatory, anti nociceptive, hepatoprotective, antithrombotic, antiviral, antibacterial and Antimicrobial agent. Although the large number of molecules known to have excellent urease inhibitory activity, there is lack of urease inhibitor drugs on the market.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Coumarinylthiazolyl Iminothiazolidinone Hybrids as Potent Urease Inhibitors

et al. 2020

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The present paper is designed to explore the potential of an important class of heterocycles coumarinylthiazolyl iminothiazolidinone to inhibit jack bean urease. The final products 6a-j were prepared by condensation of substituted aldehydes with intermediate 5 in sodium methoxide/methanol mixture. The synthesized compounds were characterized by their FTIR, 1 H, 13 C NMR and mass spectral data. The synthesized coumarinylthiazolyl iminothiazolidinone hybrids 6 a-j were evaluated for their potential to inhibit urease activity. All the synthesized derivatives showed remarkable inhibitory activity with IC 50 ranging 8 to 34 nM, while IC 50 of standard thiourea is 18.5 nM. The compound 5-(2,4-Dichlorobenzylidene)-2-(4-(2-oxo-2Hchromen-3-yl)thiazol-2-yl imino) thiazolidin-4-one 6 h bearing 2,4-di-chloro substituted phenyl ring exhibited excellent activity with IC 50 value 8 nM. In silico molecular docking studies was performed against urease enzyme PDBID 4H9 M and predicted possible binding modes in catalytic site for these active compounds. The thiazole nitrogen in compound 6 h formed a strong hydrogen bonding interaction with side chain Gln635 having distance 2.01 Å and rest part of this inhibitor is present close to Val640. The most potent derivative 6 h have highest binding affinity with binding energy À 6.178 kcal/mol. It is concluded based upon our results that 6 a and 6 h are most promising compounds from this series and provide a basis for rationale design of most potent urease inhibitors.

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Design, Synthesis, Antimicrobial Evaluation, and Molecular Modeling Studies of Novel Indolinedione–Coumarin Molecular Hybrids

Cited by 89 publications

References 40 publications

Coumarin‐containing hybrids and their antibacterial activities

Coumarin‐containing hybrids and their antibacterial activities

Indole/isatin‐containing hybrids as potential antibacterial agents

Synthesis, Biological Evaluation and Molecular Docking Studies of Novel Coumarinylthiazolyl Iminothiazolidinone Hybrids as Potent Urease Inhibitors

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