Design, synthesis and evaluation of biological activity of thiazole derivatives

This thesis presents and discusses the design, synthesis and evaluation ofbiological activity of twenty-two (22) novel thiazole derivatives, twelve (12) of whichare chalcones, two (2) aminopyrimidines and eight (8), N-phenylpyrazolines.Prediction of biological activity spectra for all compounds was performed bythe program PASS.The aim was to design compounds that would combine antimicrobial and antiinflammatoryactivity, taking into account the wide spectrum of biological activitiesof thiazole derivatives, as well as, the interesting pharmacological properties ofchalcones, aminopyrimidines and N-phenylpyrazolines.The final compounds were identified by elemental analysis and spectroscopicmethods.Σheoritical calculations of several physicochemical parameters, includinglipophilicity, were performed for all final compounds.The evaluation of antimicrobial activity of the compounds against selected Gram(+) and Gram (-) bacteria and fungi was carried out in vitro using microdilution method.For a number of selected compounds, DNA gyrase inhibition assay was alsoperformed, in order to explain the possible mechanism of their antibacterial activity.The in vivo evaluation of anti-inflammatory activity of compounds was carriedout by use of carrageenin induced mouse paw edema model, while selected compoundswere also tested in vitro for their ability to inhibit cycloxygenase (COX 1 and 2)

Thiazoles and Thiazolidinones as COX/LOX Inhibitors

Inflammation is a natural process that is connected to various conditions and disorders such as arthritis, psoriasis, cancer, infections, asthma, etc. Based on the fact that cyclooxygenase isoenzymes (COX-1, COX-2) are responsible for the production of prostaglandins that play an important role in inflammation, traditional treatment approaches include administration of non-steroidal anti-inflammatory drugs (NSAIDs), which act as selective or non-selective COX inhibitors. Almost all of them present a number of unwanted, often serious, side effects as a consequence of interference with the arachidonic acid cascade. In search for new drugs to avoid side effects, while maintaining high potency over inflammation, scientists turned their interest to the synthesis of dual COX/LOX inhibitors, which could provide numerous therapeutic advantages in terms of anti-inflammatory activity, improved gastric protection and safer cardiovascular profile compared to conventional NSAIDs. Τhiazole and thiazolidinone moieties can be found in numerous biologically active compounds of natural origin, as well as synthetic molecules that possess a wide range of pharmacological activities. This review focuses on the biological activity of several thiazole and thiazolidinone derivatives as COX-1/COX-2 and LOX inhibitors

Synthetic and Semisynthetic Compounds as Antibacterials Targeting Virulence Traits in Resistant Strains: A Narrative Updated Review

This narrative review paper provides an up-to-date overview of the potential of novel synthetic and semisynthetic compounds as antibacterials that target virulence traits in resistant strains. The review focused on research conducted in the last five years and investigated a range of compounds including azoles, indoles, thiophenes, glycopeptides, pleuromutilin derivatives, lactone derivatives, and chalcones. The emergence and spread of antibiotic-resistant bacterial strains is a growing public health concern, and new approaches are urgently needed to combat this threat. One promising approach is to target virulence factors, which are essential for bacterial survival and pathogenesis, but not for bacterial growth. By targeting virulence factors, it may be possible to reduce the severity of bacterial infections without promoting the development of resistance. We discuss the mechanisms of action of the various compounds investigated and their potential as antibacterials. The review highlights the potential of targeting virulence factors as a promising strategy to combat antibiotic resistance and suggests that further research is needed to identify new compounds and optimize their efficacy. The findings of this review suggest that novel synthetic and semisynthetic compounds that target virulence factors have great potential as antibacterials in the fight against antibiotic resistance

Design, Synthesis, Evaluation of Antimicrobial Activity and Docking Studies of New Thiazole-based Chalcones.

BACKGROUND Thiazole derivates as well as chalcones, are very important scaffold for medicinal chemistry. Literature survey revealed that they possess wide spectrum of biological activities among which are anti-inflammatory and antimicrobial. OBJECTIVES The current studies describe the synthesis and evaluation of antimicrobial activity of twenty eight novel thiazole-based chalcones. METHODS The designed compounds were synthesized using classical methods of organic synthesis. The in vivo evaluation of antimicrobial activity was performed by microdilution method. RESULTS All compounds have shown antibacterial properties better than that of ampicillin and in many cases better than streptomycin. As far as the antifungal activity is concerned, all compounds possess much higher activity than reference drugs bifonazole and ketoconazole. The most sensitive bacterial species was B. cereus (MIC 6.5-28.4 µmol × 10-2/mL and MBC 14.2-105.0 µmol × 10-2/mL) while the most resistant ones were L. monocytogenes (MIC 21.4-113.6 µmol × 10-2/mL) and E. coli (MIC 10.7- 113.6 µmol × 10-2/mL) and MBC at 42.7-358.6 µmol × 10-2/mL and 21.4-247.2 µmol × 10-2/mL, respectively. All the compounds exhibited antibacterial activity against the three resistant strains, MRSA, P. aeruginosa and E.coli. with MIC and MBC in the range of 0.65-11.00 µmol/mL × 10-2 and 1.30-16.50 µmol/mL × 10-2. Docking studies were performed. CONCLUSION Twenty-eight novel thiazole-based chalcones were designed, synthesized and evaluated for antimicrobial activity. The results showed that these derivatives could be lead compounds in search of new potent antimicrobial agents. Docking studies indicated that DNA gyrase, GyrB and MurA inhibition may explain the antibacterial activity