Sinteza kumarinskih heterocikličkih derivata s antioksidativnim djelovanjem i in vitro citotoksično djelovanje na tumorske stanice

The aim of the present work was to synthesise coumarinyl heterocycles and to elucidate the potential role of these compounds as antioxidants and cytotoxic agents against Dalton\u27s lymphoma ascites tumour cells (DLA) and Ehrlich ascites carcinoma cells (EAC). The synthesis of coumarin derivatives containing pyrazole, pyrazolone, thiazolidin-4-one, 5-carboxymethyl-4-thiazolidinone and 3-acetyl-1,3,4-oxadiazole ring is reported. 4-Methylcoumarinyl-7-oxyacetic acid hydrazide (1) reacted with arylazopropanes or hydrazono-3-oxobutyrate derivatives to form pyrazole (3a-c) and pyrazolone derivatives (5a-c). Heterocyclisation of Schiffs bases of 1 with thioglycolic acid, thiomalic acid or acetic anhydride afforded novel heterocyclic derivatives 4-thiazolidinones (7a-c), 5-carboxymethyl-4-thiazolidinones (8a-c) and oxadiazoles (9a-c), respectively. Some of the compounds showed promising results in in vitro antioxidant activity and cytotoxic activity against DLA cells and EAC cells.Cilj rada bio je sintetizirati kumarinske heterocikličke derivate i razjasniti njihovu potencijalnu ulogu kao antioksidativnih i citotoksičnih agenasa na tumorske stanice Daltonovog limfoma (DLA) i Ehrlichove tumorske stanice (EAC). U radu je opisana sinteza kumarinskih derivata s pirazolskim, pirazolonskim, tiazolidin-4-onskim, 5-karboksimetil-4-tiazolidinonskim i 3-acetil-1,3,4-oksadiazolskim prstenom. Hidrazid 4-metilkumarinil-7-oksioctene kiseline (1) dao je u reakciji s derivatima arilazopropana ili hidrazono-3-oksobutirata derivate pirazola (3a-c) i pirazolona (5a-c). Heterociklizacijom Schiffovih baza 1 s tioglikolnom kiselinom, tiojabučnom kiselinom ili anhidridom octene kiseline nastali su heterociklički derivati 4-tiazolidinoni (7a-c), 5-karboksimetil-4-tiazolidinoni (8a-c) i oksadiazoli (9a-c). Neki od spojeva pokazali su obećavajuće rezultate u in vitro testovima za antioksidativno i citostatsko djelovanje na DLA i EAC stanicama pokazali

Prevalence of adverse drug reactions at a private tertiary care hospital in south India

Background: Adverse Drug Reactions (ADRs) constitute an enormous burden for the society. The aim of the present study was to detect, document, assess and report the suspected ADRs and preparation of guidelines to minimize the incidence of ADRs. Methods: A prospective-observational study was conducted in the Department of General Medicine of a tertiary care hospital for 12 months from April 2008 to March 2009. Detected and suspected ADRs were analyzed for causality, se-verity and preventability using appropriate validated scales and were reported. ADR alert card was prepared and given to patients. Therapeutic guidelines were prepared and given to the relevant departments. Results: A total of 57 ADRs were detected, documented, assessed and reported during the study period the incidence was found to be 1.8%. Assessment of severity of the suspected ADRs revealed that 12% of suspected ADRs were se-vere and 49% of ADRs were moderate in severity. Causality assessment was done which revealed 63% of ADRs were possibly drug-related. The majority of patients who had suffered from ADRs were above 60 years (56%). Gastrointesti-nal system was most commonly affected (37%) and the drug class mostly associated with ADRs was antibiotics (23%). Preventability of ADRs was assessed; and the results revealed that 28% of ADRs were definitely preventable. Conclusions: Measures to improve detection and reporting of adverse drug reactions by all health care professionals is recommended to be undertaken, to ensure, and improve patient′s safety. In this way, hospital/clinical pharmacists play the cornerstone role

Impact of pharmaceutical care on quality of life in patients with type 2 diabetes mellitus

Background: Diabetes mellitus has become an international healthcare crisis that requires new approaches to prevent and treat it. The objective of this study was to evaluate the impact of pharmaceutical care on quality of life (QOL) in patients with type 2 diabetes mellitus. Methods: A prospective study on impact of pharmaceutical care on QOL in patients with type 2 diabetes mellitus was conducted in a private tertiary care teaching hospital in South India for a period of 8 months. Study was done on 120 eligible patients with type 2 diabetes mellitus enrolled randomly in the intervention group (with pharmaceutical care teachings) or the control (without drug related educations). The intervention group patients received pharmaceutical care through diabetes education, medication counseling, instructions on lifestyle that needed modifications (necessary for better drug function) and dietary regulations regarding their prescribed drugs, whereas the control group patients were deprived of any pharmaceutical care till the end of the study. The "Audit of Diabetes Dependent Quality of Life" standard questionnaire was used to assess the relevant parameters (including: Fasting Blood Glucose, HbA1c, Body Mass Index) and to evaluate the impact of the pharmaceutical care on the subjects. Data were analyzed using t-student test. Results: The intervention group showed an improvement in the quality of life score from -2.156 ± 0.12 at the baseline to -1.41 ± 0.13 at the final interview (p < 0.01). The average HbA1c values decreased from 8.44 ± 0.29% to 6.73 ± 0.21% (p < 0.01). There was a significant decrease in the fasting blood glucose from 195.57 ± 10.10 mg/dl to 107.25 ± 3.70 mg/dl between the baseline and the final interview in the intervention group (p < 0.01). The findings in the diabetes treatment satisfaction score also changed in a similar pattern. Conclusions: The pharmaceutical care program was effective in improving the clinical outcome and the patients′ QOL with type 2 diabetes mellitus

Sinteza i biološko djelovanje derivata 3-{[5-(6-metil-4-aril-2-okso-1,2,3,4-tetrahidropirimidin-5-il)-1,3,4-oksadiazol-2-il] -imino}-1,3-dihidro-2H-indol-2-ona

Reaction of ethyl-6-methyl–2-oxo-4-aryl-1,2,3,4-tetrahydropyrimidin-5-carboxylates (1a-i) with hydrazine hydrate yielded 6-methyl-2-oxo-4-aryl-1,2,3,4-tetrahydropyrimidin-5-carbohydrazides (2a-i). These products on reaction with cyanogen bromide gave 5-(5-amino-1,3,4-oxadiazol-2-yl)-6-methyl-4-aryl-3,4-dihydropyrimidin-2(1H)-one (3a-i). The resultant aminooxadiazolylpyrimidinones were condensed with isatin to obtain various 3-{[5-(6-methyl-4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl]-imino}-1,3-dihydro-2H-indol-2-ones (4a-i). These products were characterized by IR, 1H NMR, mass spectra and elemental analysis. Products 4a-i revealed promising antibacterial, antifungal and antioxidant activity.Derivati 6-metil-2-okso-4-aril-1,2,3,4-tetrahidropirimidin-5-karbohidrazida (2a-i) pripravljeni su reakcijom etil-6-metil–2-okso-4-aril-1,2,3,4-tetrahidropirimidin-5-karboksilata (1a-i) i hidrazin hidrata. Iz njih su sa cijanogen bromidom priređeni 5-(5-amino-1,3,4-oksadiazol-2-il)-6-metil-4-aril-3,4-dihidropirimidin-2(1H)-oni (3a-i). Kondenzacijom nastalih aminooksadiazolilpirimidinona s izatinom dobiveni su 3-{[5-(6-metil-4-aril-2-okso-1,2-tetrahidropirimidin-5-il)-1,3,4-oksadiazol-2-il]-imino}-1,3-dihidro-2H-indol-2-oni (4a-i). Produkti 4 karakterizirani su uobičajenim spektroskopskim metodama (IR, 1H NMR, spektar masa) i elementarnom analizom. Biološko vrednovanje ukazuje da spojevi 4a-i imaju potencijalno antibakterijsko, antimikotsko i antioksidativno djelovanje