Medicinal Chemistry

Fatty acid imaging can measure fatty acid oxidation rates in heart or liver for research applications in animals and clinical applications in humans with metabolic disorders. Recent advances in fatty acid imaging using single photon emission computed tomography (SPECT) include the wide applications of the tracer beta-methyl-p-[123I]-iodophenylpentadecanoic acid (BMIPP) to assess ischemic heart disease, cardiomyopathies, myocarditis, acute coronary syndrome, and heart failure and the design of new technetium-99m labeled tracers. In this mini-review article, several technetium-99m labeled fatty acid analogues as SPECT tracers are characterised, and the uptake of tracers, clearance from tissues, and mechanism of metabolism are discussed in detail. We subsequently summarized that some essential modification in fatty acid analogue structure can exert profound differences in the biodisposition and specificity of these tracers to improve the uptakes of fatty acids and prolong theirs retention in myocardium/hepatocyte. Thus, technetium- 99m labeled fatty acid analogues have significant potential to play an important role as clinical SPECT traces of fatty acid oxidation in cardiovascular diseases, liver, and other applications in skeletal muscle and tumors.

This article represents a mini-review dedicated to chalcone derivatives with antimycobacterial activity. Natural and synthetic chlacones are reviewed. General and specific schemes of synthesis of chalchone derivatives are presented. QSAR and docking studies of certain chalcones are analyzed in respect of their antimycobacterial activity and inhibition of Mycobacterium tuberculosis enzymes.

In this study, several novel peptidomimetics were designed and synthesized as potential anti-inflammatory agents. Their anti-inflammatory activity was evaluated using a xylene-induced ear edema model assay. Some of the compounds demonstrated inhibitory activity against xylene-induced inflammation similar to the positive control, aspirin.

Objectives: The analytical performances of the Sebia capillary electrophoresis (CE), Roche turbidimetric inhibition immunoassay (TINIA), Tosoh G8 cation-exchange high-performance liquid chromatography (HPLC) and Premier boronate affinity chromatography methods were evaluated. Capillary electrophoresis (CE) was accepted as a comparative method.
Design and Methods: This study comprised randomly chosen 224 whole blood samples from the diabetic and non-diabetic patients. HbA1c level was quantified using four methods as follows: Roche TINIA, Premier Hb9210 boronate affinity chromatography, Tosoh G8 cation-exchange HPLC and Sebia CE. The analytical performances of the methods were evaluated with imprecion, bias estimation and comparison studies.
Results: The results of all precision studies CV% were under 2.0%. The accepted goals for imprecision are 2.8% (IFCC) and <2.0% (NGSP). Analysis using Spearman test showed good correlation between CE and all three evaluated methods (r=0.99, p=0.001; r=0.98, p=0.001; and r=0.98, p=0.001, respectively). The comparison of the methods with CE was performed using Deming Regression analysis and revealed good agreement between CE and all methods. Although the HPLC method showed a linear relation with CE, it differed significantly from the comparative method because of its confidence interval did not contain 0.
Conclusion: All methods revealed acceptable precision and good accuracy. TINIA and boronate affinity chromatography methods showed good agreement and correlation with the comparative method (CE), whereas a significant difference was obtained between the mean levels of HPLC and CE.

Metabolomics is a rapidly growing field of research used in the identification and quantification of the small molecule metabolites within an organism, thereby providing insights into processes important in clinical medicine. It offers comprehensive information about thousands of low-molecular metabolites (<1500 Da) that represent a wide range of metabolism pathways. In human studies, metabolomics has been applied to define biomarkers related to prognosis or diagnosis of a disease. Pancreatic cancer is a devastating disease and has a very low 5 years-survival rate and its diagnosis is often late and imprecise due to the lack of specificity of currently used markers for pancreatic cancer. Obviously, more sensitive biomarkers for early diagnosis and treatment are urgently needed. Fortunately, metabolomics is becoming increasingly popular, and may provide clinically useful biomarkers applied toward identifying metabolic alterations in pancreatic cancer and has introduced new insights into the pathology of pancreatic cancer. By measuring the endogenous metabolites, metabolomics can be used for delineating metabolic networks and discovering metabolic markers. Studying pancreatic cancer through metabolomics could reveal new biomarkers that could be useful for its future prognosis, diagnosis and therapy. In this review we take a closer look at the metabolomics used within the field of pancreatic cancer disease diagnosis.