Preparation, COX-2 Inhibition and Anticancer Activity of Sclerotiorin Derivatives

Chen, Tao; Huang, Yucong; Hong, Junxian; Wei, Xikang; Zeng, Fang; Li, Jialin; Ye, Geting; Yuan, Jie; Long, Yuhua

doi:10.3390/md19010012

Cited by 13 publications

(7 citation statements)

References 38 publications

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“…Furthermore, the reported antitumor properties of salicylamide-containing compounds [42] , [43] , [44] prompted the current study due to the targeted salicylamide derivative formed through conjugation of the carboxylic group of aspirin with the nitrogen atom of piperidinyl heterocycle. Recent reports describing the pathophysiological role of COX-1/2 inhibitors in cancer disease and the discovered COX-2 inhibitors as antitumor also supported the rational of the current study [45] , [46] .…”

Section: Introductionsupporting

confidence: 81%

Synthesis of aspirin-curcumin mimic conjugates of potential antitumor and anti-SARS-CoV-2 properties

Srour

Panda

Mostafa

et al. 2021

Bioorganic Chemistry

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Section: Introductionsupporting

confidence: 81%

Synthesis of aspirin-curcumin mimic conjugates of potential antitumor and anti-SARS-CoV-2 properties

Srour

Panda

Mostafa

et al. 2021

Bioorganic Chemistry

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“…The results revealed that all of the synthesized Methoxyphenyl thiazolecarboxamide derivatives did not exhibit antiproliferative activity with IC 50 values higher than 40 µM concentration except compounds 2f and 2e, and this means that these compounds have no cytotoxic activities against the used cell lines at the effective dose. There is strong relationship between the COX enzyme and tumer overexprasion, the COX-2 enzyme is usually overexpressed in severl sorts of human cancers, and the biological studies consistently explained that COX-2 inhibitors compounds can inhibit the tumor progression and metastasis in several animal models of cancer [ 44 , 45 ]. However, compounds like 2f with COX inhibitory and anticancer activities could be a promising agents for both targets.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis, molecular docking studies and biological evaluation of thiazole carboxamide derivatives as COX inhibitors

et al. 2023

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Background Nonsteroidal anti-inflammatory drugs (NSAIDs) have been the most commonly used class of medications worldwide for the last three decades. Objectives This study aimed to design and synthesize a novel series of methoxyphenyl thiazole carboxamide derivatives and evaluate their cyclooxygenase (COX) suppressant and cytotoxic properties. Methods The synthesized compounds were characterized using 1H, 13C-NMR, IR, and HRMS spectrum analysis and were evaluated for their selectivity towards COX-1 and COX-2 using an in vitro COX inhibition assay kit. Besides, their cytotoxicity was evaluated using the Sulforhodamine B (SRB) assay. Moreover, molecular docking studies were conducted to identify the possible binding patterns of these compounds within both COX-1 and COX-2 isozymes, utilizing human X-ray crystal structures. The density functional theory (DFT) analysis was used to evaluate compound chemical reactivity, which was determined by calculating the frontier orbital energy of both HOMO and LUMO orbitals, as well as the HOMO–LUMO energy gap. Finally, the QiKProp module was used for ADME-T analysis. Results The results revealed that all synthesized molecules have potent inhibitory activities against COX enzymes. The percentage of inhibitory activities at 5 µM concentration against the COX2 enzyme was in the range of 53.9–81.5%, while the percentage against the COX-1 enzyme was 14.7–74.8%. That means almost all of our compounds have selective inhibition activities against the COX-2 enzyme, and the most selective compound was 2f, with selectivity ratio (SR) value of 3.67 at 5 µM concentration, which has a bulky group of trimethoxy on the phenyl ring that could not bind well with the COX-1 enzyme. Compound 2h was the most potent, with an inhibitory activity percentage at 5 µM concentration of 81.5 and 58.2% against COX-2 and COX-1, respectively. The cytotoxicity of these compounds was evaluated against three cancer cell lines: Huh7, MCF-7, and HCT116, and negligible or very weak activities were observed for all of these compounds except compound 2f, which showed moderate activities with IC50 values of 17.47 and 14.57 µM against Huh7 and HCT116 cancer cell lines, respectively. Analysis of the molecular docking suggests 2d, 2e, 2f, and 2i molecules were bound to COX-2 isozyme favorably over COX-1 enzyme, and their interaction behaviors within COX-1 and COX-2 isozymes were comparable to celecoxib, as an ideal selective COX-2 drug, which explained their high potency and COX-2 selectivity. The molecular docking scores and expected affinity using the MM-GBSA approach were consistent with the recorded biological activity. The calculated global reactivity descriptors, such as HOMO and LUMO energies and the HOMO–LUMO gaps, confirmed the key structural features required to achieve favorable binding interactions and thus improve affinity. The in silico ADME-T studies asserted the druggability of molecules and have the potential to become lead molecules in the drug discovery process. Conclusion In general, the series of the synthesized compounds had a strong effect on both enzymes (COX-1 and COX-2) and the trimethoxy compound 2f was more selective than the other compounds.

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“…Because the crystal structure of glucosidase from Saccharomyces cerevisiae cannot be obtained, the α-glucosidase homology model (PDB:3AXH) provided by SWISSMODEL Repository was used, and the model quality was evaluated [ 29 ]. The α-glucosidase homology model (PDB:3AXH) with compounds 1 – 5 was performed on Autodock, as described previously [ 31 , 32 , 33 , 34 ].…”

Section: Methodsmentioning

confidence: 99%

Secondary Metabolites with α-Glucosidase Inhibitory Activity from Mangrove Endophytic Fungus Talaromyces sp. CY-3

et al. 2021

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Eight new compounds, including two sambutoxin derivatives (1–2), two highly oxygenated cyclopentenones (7–8), four highly oxygenated cyclohexenones (9–12), together with four known sambutoxin derivatives (3–6), were isolated from semimangrove endophytic fungus Talaromyces sp. CY-3, under the guidance of molecular networking. The structures of new isolates were elucidated by analysis of detailed spectroscopic data, ECD spectra, chemical hydrolysis, 13C NMR calculation, and DP4+ analysis. In bioassays, compounds 1–5 displayed better α-glucosidase inhibitory activity than the positive control 1-deoxynojirimycin (IC50 = 80.8 ± 0.3 μM), and the IC50 value was in the range of 12.6 ± 0.9 to 57.3 ± 1.3 μM.

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Preparation, COX-2 Inhibition and Anticancer Activity of Sclerotiorin Derivatives

Cited by 13 publications

References 38 publications

Synthesis of aspirin-curcumin mimic conjugates of potential antitumor and anti-SARS-CoV-2 properties

Synthesis of aspirin-curcumin mimic conjugates of potential antitumor and anti-SARS-CoV-2 properties

Design, synthesis, molecular docking studies and biological evaluation of thiazole carboxamide derivatives as COX inhibitors

Secondary Metabolites with α-Glucosidase Inhibitory Activity from Mangrove Endophytic Fungus Talaromyces sp. CY-3

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