Discovery of new 2-(3-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazole derivatives with potential analgesic and anti-inflammatory activities: In vitro, in vivo and in silico investigations
Bioorg Chem. 2024 Apr 17;147:107372. doi: 10.1016/j.bioorg.2024.107372. Online ahead of print.ABSTRACTJoining the global demand for the discovery of potent NSAIDs with minimized ulcerogenic effect, new pyrazole clubbed thiazole derivatives 5a-o were designed and synthesized. The new derivatives were initially evaluated for their analgesic activity. Eight compounds 5a, 5c, 5d, 5e, 5f, 5h, 5m, and 5o showed higher activity than Indomethacin (potency = 105-130 % vs. 100 %). Subsequently, they were picked for further evaluation of their anti-inflammatory activity, ulcerogenic liability as well as toxicological studies. Derivat...
Source: Bioorganic Chemistry - April 23, 2024 Category: Chemistry Authors: Eman R Mohammed Aliaa H Abd-El-Fatah Abdalla R Mohamed Marianne A Mahrouse Mohammad A Mohammad Source Type: research
Celecoxib and sulindac sulfide elicit anticancer effects on PIK3CA-mutated head and neck cancer cells through endoplasmic reticulum stress, reactive oxygen species, and mitochondrial dysfunction
Biochem Pharmacol. 2024 Apr 18;224:116221. doi: 10.1016/j.bcp.2024.116221. Online ahead of print.ABSTRACTGain-of-function mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit alpha gene (PIK3CA) is a significant factor in head and neck cancer (HNC). Patients with HNC harboring PIK3CA mutations receive therapeutic benefits from the use of non-steroidal anti-inflammatory drugs (NSAIDs). However, the molecular mechanisms underlying these effects remain unknown. Here, we examined the Detroit562 and FaDu cell lines as HNC models with and without a hyperactive PIK3CA mutation (H1047R), respecti...
Source: Biochemical Pharmacology - April 19, 2024 Category: Drugs & Pharmacology Authors: Nga Thi Thanh Nguyen Sang Yoon Lee Source Type: research
Exploration of isoxazole analogs: Synthesis, COX inhibition, anticancer screening, 3D multicellular tumor spheroids, and molecular modeling
In this study, a new series of Isoxazole-carboxamide derivatives were synthesized and characterized via HRMS, 1H-, 13CAPT-NMR, and MicroED. The findings revealed that nearly all of the synthesized derivatives exhibited potent inhibitory activities against both COX enzymes, with IC50 values ranging from 4.1 nM to 3.87 μM. Specifically, MYM1 demonstrated the highest efficacy among the compounds tested against the COX-1, displaying an IC50 value of 4.1 nM. The results showed that 5 compounds possess high COX-2 isozyme inhibitory effects with IC50 value in range 0.24-1.30 μM with COX-2 selectivity indexes (2.51-6.13), among ...
Source: European Journal of Medicinal Chemistry - April 16, 2024 Category: Chemistry Authors: Mohammed Hawash Samer Abdallah Mahmoud Abudayyak Yarob Melhem Mohammed Abu Shamat Meera Aghbar Irfan Çapan Murad Abualhasan Anil Kumar Micha ł Kamiński Tomasz G óral Paulina Maria Dominiak Shorooq Sobuh Source Type: research
Exploration of isoxazole analogs: Synthesis, COX inhibition, anticancer screening, 3D multicellular tumor spheroids, and molecular modeling
In this study, a new series of Isoxazole-carboxamide derivatives were synthesized and characterized via HRMS, 1H-, 13CAPT-NMR, and MicroED. The findings revealed that nearly all of the synthesized derivatives exhibited potent inhibitory activities against both COX enzymes, with IC50 values ranging from 4.1 nM to 3.87 μM. Specifically, MYM1 demonstrated the highest efficacy among the compounds tested against the COX-1, displaying an IC50 value of 4.1 nM. The results showed that 5 compounds possess high COX-2 isozyme inhibitory effects with IC50 value in range 0.24-1.30 μM with COX-2 selectivity indexes (2.51-6.13), among ...
Source: Molecular Medicine - April 16, 2024 Category: Molecular Biology Authors: Mohammed Hawash Samer Abdallah Mahmoud Abudayyak Yarob Melhem Mohammed Abu Shamat Meera Aghbar Irfan Çapan Murad Abualhasan Anil Kumar Micha ł Kamiński Tomasz G óral Paulina Maria Dominiak Shorooq Sobuh Source Type: research
Exploration of isoxazole analogs: Synthesis, COX inhibition, anticancer screening, 3D multicellular tumor spheroids, and molecular modeling
In this study, a new series of Isoxazole-carboxamide derivatives were synthesized and characterized via HRMS, 1H-, 13CAPT-NMR, and MicroED. The findings revealed that nearly all of the synthesized derivatives exhibited potent inhibitory activities against both COX enzymes, with IC50 values ranging from 4.1 nM to 3.87 μM. Specifically, MYM1 demonstrated the highest efficacy among the compounds tested against the COX-1, displaying an IC50 value of 4.1 nM. The results showed that 5 compounds possess high COX-2 isozyme inhibitory effects with IC50 value in range 0.24-1.30 μM with COX-2 selectivity indexes (2.51-6.13), among ...
Source: European Journal of Medicinal Chemistry - April 16, 2024 Category: Chemistry Authors: Mohammed Hawash Samer Abdallah Mahmoud Abudayyak Yarob Melhem Mohammed Abu Shamat Meera Aghbar Irfan Çapan Murad Abualhasan Anil Kumar Micha ł Kamiński Tomasz G óral Paulina Maria Dominiak Shorooq Sobuh Source Type: research
Molecules, Vol. 29, Pages 1802: Design and Evaluation of NSAID Derivatives as AKR1C3 Inhibitors for Breast Cancer Treatment through Computer-Aided Drug Design and In Vitro Analysis
Pulido
Breast cancer is a major global health issue, causing high incidence and mortality rates as well as psychological stress for patients. Chemotherapy resistance is a common challenge, and the Aldo-keto reductase family one-member C3 enzyme is associated with resistance to anthracyclines like doxorubicin. Recent studies have identified celecoxib as a potential treatment for breast cancer. Virtual screening was conducted using a quantitative structure–activity relationship model to develop similar drugs; this involved backpropagation of artificial neural networks and structure-based virtual screening. ...
Source: Molecules - April 16, 2024 Category: Chemistry Authors: Victoria Fonseca-Ben ítez Paola Acosta-Guzm án Juan Esteban S ánchez Zaira Alarc ón Ronald Andr és Jiménez James Guevara-Pulido Tags: Article Source Type: research
Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis
This study aimed to identify drivers of PGE2 and its role in the inadvertent MSC misdifferentiation into hypertrophic chondrocytes. PGE2 release, which rose in the first three weeks of MSC chondrogenesis, was jointly stimulated by endogenous BMP, WNT, and hedgehog activity that supported the exogenous stimulation by TGF-β1 and insulin to overcome the PGE2 inhibition by dexamethasone. Experiments with PGE2 treatment or the inhibitor celecoxib or specific receptor antagonists demonstrated that PGE2, although driven by prohypertrophic signals, exerted broad autocrine antihypertrophic effects. This chondroprotective effect ma...
Source: European Journal of Cell Biology - April 12, 2024 Category: Cytology Authors: Sven Schmidt Felicia A M Klampfleuthner Tobias Renkawitz Solvig Diederichs Source Type: research
Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis
This study aimed to identify drivers of PGE2 and its role in the inadvertent MSC misdifferentiation into hypertrophic chondrocytes. PGE2 release, which rose in the first three weeks of MSC chondrogenesis, was jointly stimulated by endogenous BMP, WNT, and hedgehog activity that supported the exogenous stimulation by TGF-β1 and insulin to overcome the PGE2 inhibition by dexamethasone. Experiments with PGE2 treatment or the inhibitor celecoxib or specific receptor antagonists demonstrated that PGE2, although driven by prohypertrophic signals, exerted broad autocrine antihypertrophic effects. This chondroprotective effect ma...
Source: European Journal of Cell Biology - April 12, 2024 Category: Cytology Authors: Sven Schmidt Felicia A M Klampfleuthner Tobias Renkawitz Solvig Diederichs Source Type: research
Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis
This study aimed to identify drivers of PGE2 and its role in the inadvertent MSC misdifferentiation into hypertrophic chondrocytes. PGE2 release, which rose in the first three weeks of MSC chondrogenesis, was jointly stimulated by endogenous BMP, WNT, and hedgehog activity that supported the exogenous stimulation by TGF-β1 and insulin to overcome the PGE2 inhibition by dexamethasone. Experiments with PGE2 treatment or the inhibitor celecoxib or specific receptor antagonists demonstrated that PGE2, although driven by prohypertrophic signals, exerted broad autocrine antihypertrophic effects. This chondroprotective effect ma...
Source: European Journal of Cell Biology - April 12, 2024 Category: Cytology Authors: Sven Schmidt Felicia A M Klampfleuthner Tobias Renkawitz Solvig Diederichs Source Type: research
Cause and chondroprotective effects of prostaglandin E2 secretion during mesenchymal stromal cell chondrogenesis
This study aimed to identify drivers of PGE2 and its role in the inadvertent MSC misdifferentiation into hypertrophic chondrocytes. PGE2 release, which rose in the first three weeks of MSC chondrogenesis, was jointly stimulated by endogenous BMP, WNT, and hedgehog activity that supported the exogenous stimulation by TGF-β1 and insulin to overcome the PGE2 inhibition by dexamethasone. Experiments with PGE2 treatment or the inhibitor celecoxib or specific receptor antagonists demonstrated that PGE2, although driven by prohypertrophic signals, exerted broad autocrine antihypertrophic effects. This chondroprotective effect ma...
Source: European Journal of Cell Biology - April 12, 2024 Category: Cytology Authors: Sven Schmidt Felicia A M Klampfleuthner Tobias Renkawitz Solvig Diederichs Source Type: research
Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on the progression of structural damage in the spine over 2 years in patients with radiographic axial spondyloarthritis from the randomised-controlled CONSUL trial
Conclusions
Combination therapy with GOL+CEL did not demonstrate statistically significant superiority over GOL monotherapy in retarding radiographic spinal progression over 2 years in r-axSpA. (Source: Annals of the Rheumatic Diseases)
Source: Annals of the Rheumatic Diseases - April 11, 2024 Category: Rheumatology Authors: Proft, F., Torgutalp, M., Muche, B., Rios Rodriguez, V., Listing, J., Protopopov, M., Rademacher, J., Haibel, H., Spiller, L., Weber, A.-K., Verba, M., Brandt-Juergens, J., Kiltz, U., Sieburg, M., Jacki, S., Sieper, J., Poddubnyy, D. Tags: Open access, ARD Lay summaries, ARD, Spondyloarthritis Source Type: research
Comparison of Pain Management Strategies to Reduce Opioid Use Postoperatively in Free Flap Breast Reconstruction: Pain Catheter versus Nerve Block in Addition to Refinements in the Oral Pain Management Regime
Conclusion Introduction of the CP reduced opioid use and LOS was shorter.PMID:38596158 | PMC:PMC11001454 | DOI:10.1055/s-0043-1777673 (Source: Archives of Plastic Surgery)
Source: Archives of Plastic Surgery - April 10, 2024 Category: Cosmetic Surgery Authors: Andrea B Stefansdottir Luis Vieira Arni Johnsen Daniel Isacson Andres Rodriguez Maria Mani Source Type: research
