4-Fluorophenylhydrazones as potential COX-2 inhibitors: a novel, efficient, one pot solid phase synthesis, docking study and pharmacological evaluation

Kumar, Vinod; Gupta, Girish Kumar; Kaur, Kiranjeet; Singh, Randhir

doi:10.1007/s00044-013-0566-8

Cited by 11 publications

(4 citation statements)

References 48 publications

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“…Arg 120 and Tyr 355 are the important parts of amino acid residues of the active site of the COX-2 enzyme and have a major role as the gateway entry of the ligand to the active site of the enzyme and initiation of the inhibitory effect. 44 The hydrogen bonds in these residues are associated with better COX-2 inhibitory activity. Compound 5 was located in an area bounded by several amino acid residues, such as Trp 385 , Trp 387 , Phe 518 , Val 523 , His 90 , Leu 352 , Leu 531 , Ala 527 , Val 349 , Gly 526 , and Ser 530 (image not displayed), and these positions were similar to the inhibitor of COX-2, SC558.…”

Section: Resultsmentioning

confidence: 99%

Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

Miladiyah

Jumina²,

Haryana³

et al. 2018

DDDT

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BackgroundXanthone derivatives have a wide range of pharmacological activities, such as those involving antibacterial, antiviral, antimalarial, anthelmintic, anti-inflammatory, antiprotozoal, and anticancer properties. Among these, we investigated the anticancer properties of xanthone. This research aimed to analyze the biological activity of ten novel xanthone derivatives, to investigate the most contributing-descriptors for their cytotoxic activities, and to examine the possible mechanism of actions of xanthone compound through molecular docking.Materials and methodsThe cytotoxic tests were carried out on WiDR and Vero cell lines, by a 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay method. The structural features required for xanthone’s anticancer activity were conducted by using the semi-empirical Austin Model-1 method, and continued with quantitative structure-activity relationship (QSAR) analysis using BuildQSAR program. The study of the possible mechanism of actions of the selected xanthone compound was done through molecular docking with PLANTS.ResultsThe three novel xanthone derivatives (compounds 5, 7, and 8) exhibited cytotoxic activity with compound 5 showed the highest degree of cytotoxicity at concentration 9.23 µg/mL (37.8 µM). The following best equation model was obtained from the BuildQSAR calculation: log 1/IC50 = −8.124 qC1 −35.088 qC2 −6.008 qC3 + 1.831 u + 0.540 logP −9.115 (n = 10, r = 0.976, s = 0.144, F = 15.920, Q2 = 0.651, SPRESS = 0.390). This equation model generated 15 proposed new xanthone compounds with better-predicted anticancer activities. A molecular docking study of compound 5 showed that xanthone formed binding interactions with some receptors involved in cancer pathology, including telomerase, tumor-promoting inflammation (COX-2), and cyclin-dependent kinase-2 (CDK2) inhibitor.ConclusionThe results suggested that compound 5 showed the best cytotoxic activity among the xanthone derivatives tested. QSAR analysis showed that the descriptors contributed to xanthone’s cytotoxic activity were the net atomic charge at qC1, qC2, and qC3 positions, also dipole moment and logP. Compound 5 was suspected to be cytotoxic by its inhibition of telomerase, COX-2, and CDK2 receptors.

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Section: Resultsmentioning

confidence: 99%

Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

Miladiyah

Jumina²,

Haryana³

et al. 2018

DDDT

View full text Add to dashboard Cite

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“…Follow-up of the reactions and checking the purity of the compounds were carried out using TLC on silica gel-precoated aluminum sheets (Fluorescent indicator 254 nm, Fluka, Germany) and the spots were detected by exposure to UV lamp at λ 254/366 nm for a few seconds or under iodine vapor. Compounds 2-(4-fluorphenylazo)malononitrile 2a and 3,5-diamino-4-(4-fluorophenylazo)-1 H -pyrazole 4b were prepared according to the reported procedure [21,22,23].…”

Section: Methodsmentioning

confidence: 99%

Synthesis, In Vitro Antimicrobial and Cytotoxic Activities of Some New Pyrazolo[1,5-a]pyrimidine Derivatives

et al. 2019

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A new series of pyrazole 4–7 and pyrazolo[1,5-a]pyrimidine 8–13 were synthesized by using a simple, efficient procedure, and screened for their in-vitro antimicrobial and antitumor activities. Symmetrical and asymmetrical 3,6-diarylazo-2,5,7-triaminopyrazolo[1,5-a]pyrimidine were synthesized by the conventional method and also subjected to microwave irradiation and under ultrasound conditions. The biological results revealed that most of the tested compounds proved to be active as antibacterial and antifungal agents. The antitumor activity of the synthesized compounds was evaluated against human cancer cell lines, MCF-7, HCT-116, and HepG-2, as compared with Doxorubicin as a control.

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“…Second, the region located at the active site gate consists of hydrophilic amino acid residues Arg120, Glu524, and Tyr355, while the third is a site pocket consisted of amino acids His90, Arg513, and Val523 (Krishna et al, 2013). Arg120 and Tyr355 are the important amino acid residue components of the COX-2 enzyme's active site and play a significant role as the ligand's gateway to the enzyme's active site, and then the inhibitory effect is initiated (Kumar et al, 2013). The interaction of native ligands (indomethacin and SC-558) with the COX-2 enzyme's active site occupied these three regions could be seen in Figures 5a and 5b.…”

Section: Docking Study Of Newly Design Chalcones Derivativesmentioning

confidence: 99%

Design of New Chlorochalcone Derivatives as Potential Breast Anticancer Compound Based on QSAR Analysis and Molecular Docking Study

Puspitasari

Pranowo

Astuti

et al. 2021

CMUJNS

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Quantitative structure-activity relationships (QSAR) proposes a model that relates the biological activities of drugs to their chemical structures, and the interaction between the drug and its target enzyme is revealed by molecular docking research. These studies were conducted on chalcone to produce a model that could design highly potent breast anticancer MCF7 cells. The compounds were optimized using ab initio using a basis set 6-31G, then their descriptors calculated using this method. Genetic Function Algorithm (GFA) was used to select descriptors and build the model. One of the six models generated was found to be the best with internal and external squared correlation coefficient (R2) of 0.743 and 0.744, respectively, adjusted squared correlation coefficient (adjusted R2) of 0.700, Standard estimate of error (SEE) of 0.198, Fcalc/Ftable of 6.423, and Predicted residual sum of squares (PRESS) of 1.177. The QSAR equation is pIC50 = 3.869 + (1.427 x qC1) + (4. 027 x qC10) + (0.856 x qC15) - (35.900 x ELUMO) + (0.208 x Log P). Hence, it can predict the breast anticancer activities of new chlorochalcones A-F. The compound with the best prediction was chlorochalcone A with pIC50 2.65 and IC50 value of 2.26 μM. The chlorochalcones A-F were able to bind to the main amino acid residues, namely Arg120 and Tyr355, on the active site of the COX-2 enzyme. These results could serve as a model for designing novel chlorochalcone as inhibitors of COX-2 with higher breast anticancer activities. Keywords: Chlorochalcone, COX-2, QSAR, MCF-7, Molecular docking

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4-Fluorophenylhydrazones as potential COX-2 inhibitors: a novel, efficient, one pot solid phase synthesis, docking study and pharmacological evaluation

Cited by 11 publications

References 48 publications

Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

Synthesis, In Vitro Antimicrobial and Cytotoxic Activities of Some New Pyrazolo[1,5-a]pyrimidine Derivatives

Design of New Chlorochalcone Derivatives as Potential Breast Anticancer Compound Based on QSAR Analysis and Molecular Docking Study

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4-Fluorophenylhydrazones as potential COX-2 inhibitors: a novel, efficient, one pot solid phase synthesis, docking study and pharmacological evaluation

Cited by 11 publications

References 48 publications

Biological activity, quantitative structure&ndash;activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

Biological activity, quantitative structure&ndash;activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

Synthesis, In Vitro Antimicrobial and Cytotoxic Activities of Some New Pyrazolo[1,5-a]pyrimidine Derivatives

Design of New Chlorochalcone Derivatives as Potential Breast Anticancer Compound Based on QSAR Analysis and Molecular Docking Study

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Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs

Biological activity, quantitative structure–activity relationship analysis, and molecular docking of xanthone derivatives as anticancer drugs