Identification of quinoline-chalcones and heterocyclic chalcone-appended quinolines as broad-spectrum pharmacological agents

Dorababu, Atukuri; Vijayalaxmi, S.; Sanjeevamurthy, R; Vidya, L; Prasannakumar, R; M.M, Raghavendra

doi:10.1016/j.bioorg.2020.104419

Cited by 22 publications

(11 citation statements)

References 53 publications

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“…Makafe et al recently, identified a novel class of quinoline derivatives as potent antituberculosis inhibitors. Their identified compounds were able to kill Mycobacterium tuberculosis by activating glutamate kinases protein 44 . Quinoline compounds have reportedly been shown to exhibit alluring pharmacological characteristics.…”

Section: Resultsmentioning

confidence: 99%

“…Their identified compounds were able to kill Mycobacterium tuberculosis by activating glutamate kinases protein. 44 Quinoline compounds have reportedly been shown to exhibit alluring pharmacological characteristics. The quinoline analogs have been used in therapeutic settings for a variety of illnesses, including cancer prevention, antibacterial and antifungal action, antiplasmodial activity, and DNA damage prevention.…”

Section: Compmentioning

confidence: 99%

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Identification of potent BRD4‐BD1 inhibitors using classical and steered molecular dynamics based free energy analysis

Gupta,

Purohit

2024

J of Cellular Biochemistry

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In the present work a combination of traditional and steered molecular dynamics based techniques were employed to identify potential inhibitors against the human BRD4 protein (BRD4‐ BD1); an established drug target for multiple illnesses including various malignancies. Quinoline derivatives that were synthesized in‐house were tested for their potential as new BRD4‐BD1 inhibitors. Initially molecular docking experiments were performed to determine the binding poses of BRD4‐BD1 inhibitors. To learn more about the thermodynamics of inhibitor binding to the BRD4‐BD1 active site, the Molecular Mechanics Poisson‐Boltzmann Surface Area (MM‐PBSA) free energy calculations were conducted afterwards. The findings of the MM‐PBSA analysis were further reinforced by performing steered umbrella sampling simulations which revealed crucial details about the binding/unbinding process of the most potent quinoline derivatives at the BRD4‐BD1 active site. We report a novel quinoline derivative which can be developed into a fully functional BRD4‐BD1 inhibitor after experimental validation. The identified compound (4 g) shows better properties than the standard BRD4‐BD1 inhibitors considered in the study. The study also highlights the crucial role of Gln78, Phe79, Trp81, Pro82, Phe83, Gln84, Gln85, Val87, Leu92, Leu94, Tyr97, Met105, Cys136, Asn140, Ile146 and Met149 in inhibitor binding. The study provides a possible lead candidate and key amino acids involved in inhibitor recognition and binding at the active site of BRD4‐BD1 protein. The findings might be of significance to medicinal chemists involved in the development of potent BRD4‐BD1 inhibitors.

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Section: Resultsmentioning

confidence: 99%

Section: Compmentioning

confidence: 99%

Identification of potent BRD4‐BD1 inhibitors using classical and steered molecular dynamics based free energy analysis

Gupta,

Purohit

2024

J of Cellular Biochemistry

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“…On top of this, many researchers are exhaustively devoted to synthesizing a chalcone derivative incorporating a heterocyclic scaffold. Chalcones incorporating heterocyclic scaffolds have been reported with various biological and pharmacological activities, such as antioxidant activity, 12 antibacterial activity, 12 antifungal activity, 13 antileishmanial activity, 14 anti-inflamatory activity, 15 anticancer activity, 16 antitubercular activity, 17 antiproliferative agents, 17 antimalarial activity, 18 antiplatelet activity, 19 carbonic anhydrase inhibitors, 20 an inhibitor of microsomalenzyme glutathione-S-transferases, 21 and CYP1 enzyme inhibitors. 22 Chalcones with an N-heterocyclic moiety such as pyrrole, imidazole, thiazole, pyrazole, oxazole, isooxazole, pyridine, pyrazoline, indole, benzothiazole, benzimidazole, and quinoline scaffolds play a significant role in the area of medicine.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis and Pharmacological Activities of Chalcone and Its Derivatives Bearing N-Heterocyclic Scaffolds: A Review

2023

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The incorporation of heterocyclic moieties into the standard chemical structure with a biologically active scaffold has become of crucial practice for the construction of pharmacologically potent candidates in the drug arena. Currently, numerous kinds of chalcones and their derivatives have been synthesized using the incorporation of heterocyclic scaffolds, especially chalcones bearing heterocyclic moieties that display improved efficiency and potential for drug production in pharmaceutical sectors. The current Review focuses on recent advances in the synthetic approaches and pharmacological activities such as antibacterial, antifungal, antitubercular, antioxidant, antimalarial, anticancer, antiinflammatory, antigiardial, and antifilarial activities of chalcone derivatives incorporating N-heterocyclic moieties at either the A-ring or B-ring.

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“…In addition, it is well documented that the combination of the quinoline ring and the chalcone moiety into a single molecular entity results in promising molecular hybrids which are useful intermediates in the design and development of new potential multitarget drugs (Atukuri et al, 2020;Mohamed & Abuo-Rahma, 2020). This class of conjugated compounds are known to possess remarkable antibacterial (Zheng et al, 2011;Rao et al, 2017), antifungal (Rao et al, 2017), antimalarial (Domı ´nguez et al, 2005;Dave et al, 2009), analgesic (Chabukswar et al, 2016), anti-VIH (Chabukswar et al, 2016) and anticancer (Kotra et al, 2010;Mohamed & Abuo-Rahma, 2020) activities.…”

Section: Introductionmentioning

confidence: 99%

A three-step pathway from (2-aminophenyl)chalcones to novel styrylquinoline–chalcone hybrids: synthesis and spectroscopic and structural characterization of three examples

et al. 2023

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Three new styrylquinoline–chalcone hybrids have been synthesized using a three-step pathway starting with Friedländer cyclocondensation between (2-aminophenyl)chalcones and acetone to give 2-methyl-4-styrylquinolines, followed by selective oxidation to the 2-formyl analogues, and finally Claisen–Schmidt condensation between the formyl intermediates and 1-acetylnaphthalene. All intermediates and the final products have been fully characterized by IR and 1H/13C NMR spectroscopy, and by high-resolution mass spectrometry, and the three products have been characterized by single-crystal X-ray diffraction. The molecular conformations of (E)-3-{4-[(E)-2-phenylethenyl]quinolin-2-yl}-1-(naphthalen-1-yl)prop-2-en-1-one, C30H21NO, (IVa), and (E)-3-{4-[(E)-2-(4-fluorophenyl)ethenyl]quinolin-2-yl}-1-(naphthalen-1-yl)prop-2-en-1-one, C30H20FNO, (IVb), are very similar. In each compound, the molecules are linked into a three-dimensional array by hydrogen bonds, of the C—H...O and C—H...N types in (IVa), and of the C—H...O and C—H...π types in (IVb), and by two independent π–π stacking interactions. By contrast, the conformation of the chalcone unit in (E)-3-{4-[(E)-2-(2-chlorophenyl)ethenyl]quinolin-2-yl}-1-(naphthalen-1-yl)prop-2-en-1-one, C30H20ClNO, (IVc), differs from those in (IVa) and (IVb). There are only weak hydrogen bonds in the structure of (IVc), but a single rather weak π–π stacking interaction links the molecules into chains. Comparisons are made with some related structures.

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Identification of quinoline-chalcones and heterocyclic chalcone-appended quinolines as broad-spectrum pharmacological agents

Cited by 22 publications

References 53 publications

Identification of potent BRD4‐BD1 inhibitors using classical and steered molecular dynamics based free energy analysis

Identification of potent BRD4‐BD1 inhibitors using classical and steered molecular dynamics based free energy analysis

Synthesis and Pharmacological Activities of Chalcone and Its Derivatives Bearing N-Heterocyclic Scaffolds: A Review

A three-step pathway from (2-aminophenyl)chalcones to novel styrylquinoline–chalcone hybrids: synthesis and spectroscopic and structural characterization of three examples

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