6 results on '"Hafedh Kochkar"'
Search Results
2. Identification of Novel Cyclooxygenase-1 Selective Inhibitors of Thiadiazole-Based Scaffold as Potent Anti-Inflammatory Agents with Safety Gastric and Cytotoxic Profile
- Author
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Michelyne Haroun, Maria Fesatidou, Anthi Petrou, Christophe Tratrat, Panagiotis Zagaliotis, Antonis Gavalas, Katharigatta N. Venugopala, Hafedh Kochkar, Promise M. Emeka, Nancy S. Younis, Dalia Ahmed Elmaghraby, Mervt M. Almostafa, Muhammad Shahzad Chohan, Ioannis S. Vizirianakis, Aliki Papadimitriou-Tsantarliotou, and Athina Geronikaki
- Subjects
molecular modeling ,thiadiazole ,enzyme inhibition ,anti-inflammatory ,ulcerogenic effect ,cyclooxygenase ,Organic chemistry ,QD241-441 - Abstract
Major obstacles faced by the use of nonsteroidal anti-inflammatory drugs (NSAID) are their gastrointestinal toxicity induced by non-selective inhibition of both cyclooxygenases (COX) 1 and 2 and their cardiotoxicity associated with a certain class of COX-2 selective inhibitors. Recent studies have demonstrated that selective COX-1 and COX-2 inhibition generates compounds with no gastric damage. The aim of the current study is to develop novel anti-inflammatory agents with a better gastric profile. In our previous paper, we investigated the anti-inflammatory activity of 4-methylthiazole-based thiazolidinones. Thus, based on these observations, herein we report the evaluation of anti-inflammatory activity, drug action, ulcerogenicity and cytotoxicity of a series of 5-adamantylthiadiazole-based thiazolidinone derivatives. The in vivo anti-inflammatory activity revealed that the compounds possessed moderate to excellent anti-inflammatory activity. Four compounds 3, 4, 10 and 11 showed highest potency (62.0, 66.7, 55.8 and 60.0%, respectively), which was higher than the control drug indomethacin (47.0%). To determine their possible mode of action, the enzymatic assay was conducted against COX-1, COX-2 and LOX. The biological results demonstrated that these compounds are effective COX-1 inhibitors. Thus, the IC50 values of the three most active compounds 3, 4 and 14 as COX-1 inhibitors were 1.08, 1.12 and 9.62 μΜ, respectively, compared to ibuprofen (12.7 μΜ) and naproxen (40.10 μΜ) used as control drugs. Moreover, the ulcerogenic effect of the best compounds 3, 4 and 14 were evaluated and revealed that no gastric damage was observed. Furthermore, compounds were found to be nontoxic. A molecular modeling study provided molecular insight to rationalize the COX selectivity. In summary, we discovered a novel class of selective COX-1 inhibitors that could be effectively used as potential anti-inflammatory agents.
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- 2023
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3. Low temperature design of titanium dioxide anatase materials decorated with cyanuric acid for formic acid photodegradation
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Ashwaq Bin Sadi, Reem Khaled Al Bilali, Samar Abdalwahab Abubshait, and Hafedh Kochkar
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Chemistry ,QD1-999 - Abstract
The influence of cyanuric acid (CA) on the structural, textural, electronic, morphological properties and the photocatalytic activity of titanium dioxide materials (TNCA) were herein evaluated. TNCAs samples were prepared through the sol gel method. The novelty of this work that cyanuric acid; the so far most recalcitrant molecule, is used here as reservoir of nitrogen. The synthesis of TNCAs nanomaterials are performed at low temperature in presence of quaternary ammonium as co-catalyst for anatase growth. Samples were characterized by means of nitrogen adsorption-desorption isotherms at 77 K, X-ray diffraction (XRD), Infrared (ATR), Raman, diffuse reflectance ultraviolet-visible, photoluminescence (PL) and electron paramagnetic resonance (EPR) spectroscopies, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The photocatalytic activities of TNCAs and their free counterpart nanomaterials were then evaluated in the photocatalytic degradation of formic acid (FA) as model molecule under UV.X-ray and Raman show success of anatase phase formation at low temperature without any post-calcination. IR-ATR analysis confirms CA grafting onto TiO2 identified by formation of vibration band between Ti and triazine. SEM mapping shows that C, O, Ti, and N are homogeneously distributed in the nanomaterial. Nitrogen adsorption-desorption measurements at 77 K show developed textural properties; the heat of N2 adsorption seems to be affected by CA loading. PL and UV-visible spectroscopies show simultaneously (i) electron trapping by the oxygen vacancy identified by Raman spectroscopy by redshift of Eg1 mode and (ii) the hole is confined by nitrogen. Therefore, the excited electron can move from TiO2 VB to the new sublevels initiated by the introduction of nitrogen which results in quenching of the photoluminescence intensity. The photocatalytic activity of the various TNCAs nanomaterials increases versus CA loading. The highest kLH of TNCA2 (5 wt%) could be explained by short migration time conjugated with lower bulk recombination of the photogenerated electron hole. Keywords: Photocatalysis, Cyanuric acid, Nanohybrids, Formic acid, Kinetics
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- 2020
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4. Exploration of the Antimicrobial Effects of Benzothiazolylthiazolidin-4-One and In Silico Mechanistic Investigation
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Michelyne Haroun, Christophe Tratrat, Anthi Petrou, Athina Geronikaki, Marija Ivanov, Ana Ćirić, Marina Soković, Sreeharsha Nagaraja, Katharigatta Narayanaswamy Venugopala, Anroop Balachandran Nair, Heba S. Elsewedy, and Hafedh Kochkar
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thiazolidinones ,PASS ,antibacterial ,MIC/MFC ,docking ,LD-carboxypeptidase ,Organic chemistry ,QD241-441 - Abstract
Background: Infectious diseases still affect large populations causing significant morbidity and mortality. Bacterial and fungal infections for centuries were the main factors of death and disability of millions of humans. Despite the progress in the control of infectious diseases, the appearance of resistance of microbes to existing drugs creates the need for the development of new effective antimicrobial agents. In an attempt to improve the antibacterial activity of previously synthesized compounds modifications to their structures were performed. Methods: Nineteen thiazolidinone derivatives with 6-Cl, 4-OMe, 6-CN, 6-adamantan, 4-Me, 6-adamantan substituents at benzothiazole ring were synthesized and evaluated against panel of four bacterial strains S. aureus, L. monocytogenes, E. coli and S. typhimirium and three resistant strains MRSA, E. coli and P. aeruginosa in order to improve activity of previously evaluated 6-OCF3-benzothiazole-based thiazolidinones. The evaluation of minimum inhibitory and minimum bactericidal concentration was determined by microdilution method. As reference compounds ampicillin and streptomycin were used. Results: All compounds showed antibacterial activity with MIC in range of 0.12–0.75 mg/mL and MBC at 0.25–>1.00 mg/mL The most active compound among all tested appeared to be compound 18, with MIC at 0.10 mg/mL and MBC at 0.12 mg/mL against P. aeruginosa. as well as against resistant strain P. aeruginosa with MIC at 0.06 mg/mL and MBC at 0.12 mg/mL almost equipotent with streptomycin and better than ampicillin. Docking studies predicted that the inhibition of LD-carboxypeptidase is probably the possible mechanism of antibacterial activity of tested compounds. Conclusion: The best improvement of antibacterial activity after modifications was achieved by replacement of 6-OCF3 substituent in benzothiazole moiety by 6-Cl against S. aureus, MRSA and resistant strain of E. coli by 2.5 folds, while against L. monocytogenes and S. typhimirium from 4 to 5 folds.
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- 2021
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5. Kinetic Modeling for Photo-Assisted Penicillin G Degradation of (Mn0.5Zn0.5)[CdxFe2-x]O4 (x ≤ 0.05) Nanospinel Ferrites
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Omar Alagha, Noureddine Ouerfelli, Hafedh Kochkar, Munirah A. Almessiere, Yassine Slimani, Ayyar Manikandan, Abdulhadi Baykal, Ahmed Mostafa, Mukarram Zubair, and Mohammad H. Barghouthi
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nanoparticles ,photodegradation ,penicillin ,kinetic modeling ,mixed spinel ferrites ,wastewater ,Chemistry ,QD1-999 - Abstract
Penicillin G is an old and widely used antibiotic. Its persistence in the environment started to appear in many environmental samples and food chains. The removal of these emerging pollutants has been a challenging task for scientists in the last decades. The photocatalytic properties of Cd2+ doped Manganese- Zinc NSFs with chemical formula (Mn0.5Zn0.5)[CdxFe2−x]O4 (0.0 ≤ x ≤ 0.05) NSFs are herein evaluated. The Manganese- Zinc N.S.F.s nanomaterials were deeply characterized, utilizing UV-Vis (reflectance) spectroscopy, X-ray diffraction, N2 adsorption isotherm measurements, and S.E.M., SEM-EDX mapping, and T.E.M. The Kinetic model for the photodegradation of penicillin G (as a model molecule) is investigated using visible light as a source of energy. The kinetic study shows that our results fit well with the modified pseudo-first-order model. The Pen G degradation are 88.73%, 66.65%, 44.70%, 37.62% and 24.68% for x = 0.5, 0.4, 0.3, 0.2 and 0.1, respectively, against 14.68% for the free Cd spinel sample. The pseudo-rate constant is bandgap dependent. From the intra-diffusion rate constant (Kd), we developed an intra-diffusion time (τ) model, which decreases exponentially as a function of (x) and mainly shows the existence of three different domains versus cadmium coordination in spinel ferrite samples. Hence, Cadmium’s presence generates spontaneous polarization with a strong opportunity to monitor the charge separation and then open the route to a new generation of “assisted” photocatalysts under visible light.
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- 2021
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6. New Substituted 5-Benzylideno-2-Adamantylthiazol[3,2-b][1,2,4]Triazol-6(5H)ones as Possible Anti-Inflammatory Agents
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Christophe Tratrat, Michelyne Haroun, Aliki Paparisva, Charalmpos Kamoutsis, Anthi Petrou, Antonis Gavalas, Phaedra Eleftheriou, Athina Geronikaki, Katharigatta N. Venugopala, Hafedh Kochkar, and Anroop B. Nair
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anti-inflammatory ,thiazole ,triazole ,COX ,LOX ,docking ,Organic chemistry ,QD241-441 - Abstract
Background: Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects. Methods: Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenan paw edema test. COX and LOX inhibitory actions were tested using ovine COX-1, human recombinant COX-2 and soybean LOX-1, respectively. Docking analysis was performed using Autodock. Results: All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis. Conclusions: A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms.
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- 2021
- Full Text
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