Alanine racemase is a fold type III PLP-dependent amino acid racemase enzyme catalysing the conversion of l-alanine to d-alanine utilised by bacterial cell wall for peptidoglycan synthesis. As there are no known homologs in humans, it is considered as an excellent antibacterial drug target. The standard inhibitors of this enzyme include O-carbamyl-d-serine, d-cycloserine, chlorovinyl glycine, alaphosphin, etc. d-Cycloserine is indicated for pulmonary and extra pulmonary tuberculosis but therapeutic use of drug is limited due to its severe toxic effects. Toxic effects due to off-target affinities of cycloserine and other substrate analogs have prompted new research efforts to identify alanine racemase inhibitors that are not substrate analogs. In this review, an updated status of known inhibitors of alanine racemase enzyme has been provided which will serve as a rich source of structural information and will be helpful in generating selective and potent inhibitor of alanine racemase.
Three flavonoid compounds were isolated from the roots of medicinal plant Tadehagi triquetrum (L.) H.Ohashi, also known as Desmodium triquetrum (Fabaceae). On the basis of the chemical and spectral analysis, the compounds were identified as baicalein (Flavone), naringin and neohesperidin (Flavonone). To the best of our knowledge and based on the literature survey all three compounds were first time reported from this medicinal plant.
Pharmacists as vital healthcare professionals play significant role in effective medication management and their use among the patients. However the perception of community pharmacist among the public needs to be assessed for effective role and further patient care. This questionnaire based study was aimed to identify the perception of patients towards the community pharmacist in north Malabar region of Kerala, India. The questionnaire consisted of 16 questions with sections evaluating the demographic details (age, sex, marital status, education level & occupation) and the perception of patients towards the community pharmacist. The results were prepared based upon the responses obtained from 110 patients. The study respondents consisted of 51 (46.36%) adults (18-59 years) and 59 (53.63%) geriatrics (above 60 years). Based on their education level, 9 (8.18%), 35 (31.81%) and 66 (60%) participants were illiterate, secondary school and graduate holders respectively. The respondents of the study informed that the pharmacist enquired about their past medication history (58, 52.73%), any allergic reactions (21, 19.1%) and use of any herbal medication (31, 28.18%) prior to the dispensing process. The patients also responded that proper advice regarding dosage (90%), side effects (25%), storage (12%), healthy eating & exercise (10%) were also provided by the concerned pharmacist. As a matter of fact, 91 out of 110 patients thought the pharmacist service were good, 17 thought they were fairly good and 2 were of the opinion that it was poor. The pharmacy rating was evaluated as good by 32 (29.09%), fairly good by 78 (70.90%) and no respondents were of opinion that the pharmacy was poor in its service. Through this study, we found that the overall perception of patients towards the pharmacist in concerned community pharmacy setting was good. To further improvise their role, continued pharmacy education programmes, better communication skills and good professional training must be imparted among the community pharmacists.
Alanine racemase is a pyridoxal-5´-phosphate dependent bacterial enzyme that provides the essential peptidoglycan precursor D-alanine, utilized for cell wall synthesis. This enzyme is ubiquitous throughout bacteria, including Mycobacterium tuberculosis, making it an attractive target for antibacterial drug discovery. We investigated the binding mode of twenty five reported Mycobacterium tuberculosis alanine racemase inhibitors. The results obtained from molecular docking studies emphasized the importance of inhibitor interaction with Lys42, Tyr46, Arg140, His172 and Tyr175 residues at the catalytic binding pocket of alanine racemase enzyme. The predicted binding free energies showed that van der Waals and nonpolar solvation interactions are the driving force for binding of inhibitors. Molecular dynamics simulation studies of four such inhibitor-alanine racemase systems were further explored to study the inhibition mechanism. The quantum chemical parameters calculated at the B3LYP/6-31G**++ level of theory indicated that the inhibitors must have low values of the lowest unoccupied molecular orbital energy and high values of electrostatic potential for stronger interactions. We expect that this study can provide significant theoretical guidance for design of potent Mycobacterium tuberculosis alanine racemase inhibitors in future.
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