A series of thiazol-4-one/thiophene-bearing pyrazole derivatives as pharmacologically attractive cores were initially synthesized using a hybridization approach. All structures were confirmed using spectra analysis techniques (IR, 1 H NMR, and 13 C NMR). In vitro antimicrobial activities, including the minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration (MBC/MFC), and time-kill assay, were evaluated for the most active derivatives 4a, 5a, 7b, 10, and 13. These derivatives were significantly active against the tested pathogens, with compound 7b as the most active derivative (MIC values range from 0.22 to 0.25 μg/mL). In the MBC and MFC, the active target pyrazole derivatives showed -cidal activities toward the pathogenic isolates. Further, the inhibition of biofilm formation of Staphylococcus aureus and Staphylococcus epidermidis was also carried out. Additionally, these derivatives displayed significant antibiofilm potential with a superior % reduction in the biofilm formation compared with Ciprofloxacin. The target derivatives behaved synergistically with Ciprofloxacin and Ketoconazole, reducing their MICs. Hemolytic results revealed that these derivatives were nontoxic with a significantly low hemolytic activity (%lysis range from 3.23 to 15.22%) compared with Triton X-100 and showed noncytotoxicity activity with IC 50 values > 60 μM. In addition, these derivatives proved to be active DNA gyrase and DHFR inhibitors with IC 50 ranging between 12.27−31.64 and 0.52−2.67 μM, respectively. Furthermore, compound 7b showed bactericidal activity at different concentrations in the time-kill assay. Moreover, a gamma radiation dose of 10.0 kGy was efficient for sterilizing compound 7b and enhancing its antimicrobial activity. Finally, molecular docking simulation of the most promising derivatives exhibited good binding energy with different interactions.
Background Allergic diseases are immunological exaggerations with symptoms that may interfere with life quality. Bilastine, a novel oral second-generation H-1 antihistamine, is highly selective to H-1 receptors and has anti inflammatory properties. The present evidence regarding the drug efficacy is inconsistent. Objectives We aimed to evaluate the efficacy and safety of bilastine compared with the placebo and other active antihistamines in patients who complained either from AR or chronic urticaria. Methods We systematically searched the Medline, Scopus, Web of Science, and Cochrane databases for randomized controlled trials (RCTs) evaluating bilastine effects on symptomatic hyper histaminic allergic conditions. We collected data on total symptoms scores (TSS), total nasal symptom scores (TNSS), discomfort associated with these allergic conditions measured by visual analog score (VAS), and quality of life (QOL) for AR and urticaria. Other outcomes such as clinical global impression and safety profiles were reported as well. We pooled the studies in a random effect model using RevMan 5.4 software. Results We included 9 RCTs comprising 3801 participants. The meta-analysis revealed that bilastine was superior to placebo, improving TSS, TNSS, VAS, and QOL in AR or chronic urticaria participants. Moreover, the bilastine was comparable to active antihistamines such as cetirizine, fexofenadine, and loratadine regarding mentioned outcomes. In addition, the novel drug was safe and tolerable with no difference in the incidence of adverse events with a placebo. Conclusions Bilastine safely improved TSS in hyper histaminic allergic conditions involving nasal symptoms in AR. It decreases the discomfort associated with the disease resulting in improving the QOL of the participants.
2-(4-Oxothiazolidin-2-ylidene)acetonitrile and ethyl-2-(4-oxothiazolidin-2-ylidene)acetate (1a,b),were condensed with anthralaldehyde(1:1 molar ratio) and gave 4,5-dihydro-4-oxothiazole derivatives (2a,b).Refluxingof 2-(antharacene-9-yl-methylene) malononitrile in acetic acid with thioglycollic acid gave(3).4-Thiaz-olidinones containing bis-aryl methylidine moieties(4a-c) and (5a,b)were produced via condensation of either(2a) or (3) with aromatic aldehydes(1:1 molar ratio). Heating of (2a) with α-substituted cinnamonitriles gave the expected substituted thiazolo[3,2-a] pyridines (6a-d),(7) and (9a-c). Thiazolo [3,2-a] pyridine enamino-nitrile (6a) was refluxed with formic acid and phenyl hydrazine to form the corresponding thiazolo [3,2-a] pyridine derivatives (10) and (11) derivatives respectively.The structures of the prepared compounds were confirmed by using spectroscopic techniques; IR; 1 HNMR ; 13 C NMR and Mass spectroscopy. Also, Anibactreial and antifungal activity were evaluated for some of synthesized compounds.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.