Ethyl 7-oxo-3,5-diphenyl-1,4-diazepane-2-carboxyl­ate

The title compound, C20H22N2O3, crystallizes with two independent mol­ecules in the asymmetric unit. In both mol­ecules, the diazepane rings adopt chair conformations. The mean planes of the diazepane rings in the two molecules form dihedral angles of 71.6 (4)/40.3 (5) and 75.9 (5)/58.6 (7)° with the neighbouring benzene rings. The carbonyl-group O atoms deviate significantly from the diazepane rings, by 0.685 (14) and 0.498 (13) Å. The eth­oxy­carbonyl groups show conformational difference between two mol­ecules, as reflected in the orientation of the carbonyl O atoms and the C—C—O—C torsion angle of −179.0 (2)° in one mol­ecule and 73.2 (2)° in the other. In one molecule there is a short N—H⋯O contact that generates an S(5) ring motif. In the crystal, N—H⋯O inter­actions generate R 2 2(8) graph-set motifs and C—H⋯O inter­actions generate R 2 2(10) and R 2 2(14) graph-set motifs. C—H⋯π inter­actions also occur

IMPACT OF CONTINUOUS PATIENT COUNSELLING ON KNOWLEDGE, ATTITUDE, AND PRACTICES AND MEDICATION ADHERENCE OF DIABETIC PATIENTS ATTENDING OUTPATIENT PHARMACY SERVICES

ABSTRACTObjective: The morbidity and morbidity associated with diabetes can be drastically reduced by the knowledge about diabetes mellitus and appropriateattitude toward the disease. A study was conducted to assess the level of knowledge, attitude, and practices (KAP) and medication adherence patternsof diabetic patients and effect of pharmacist‑led patient education on KAP and medication adherence patterns in these patients.Methods: 400 diabetic patients of either sex, aged above 18 years were divided randomly into two groups of 200 each as control and the interventiongroups. At the baseline, patients in both the groups were assessed for KAP using KAP Questionnaire and medication adherence using MoriskyAdherence Questionnaire. Patients in the intervention group were counseled both verbally and by distribution of a patient education leaflets at baselineand at three consecutive follow‑ups (1st, 2nd, and 3 months), and patients in the control group were counseled both verbally and by distribution ofpatient education leaflets at the baseline and then on the follow‑up after 3 months. Both the groups were assessed repeatedly for KAP and medicationadherence using same questionnaires after each counseling sessions. The mean scores of KAP and medication adherence, and the fasting blood sugarlevels (FBS) at the baseline and on the follow‑up for control and the intervention groups were analyzed statistically using independent sample t‑testand Mann–Whitney U‑test.rdResults: Of 200 patients in each group, 178 females and 22 males in the intervention group (mean age 57.80±9.878 years) and 179 females and21 males in the control group (mean age 57.57±9.438 years). A statistically significant improvement in the mean KAP and adherence scores wasobserved from the baseline to the final follow‑up in both groups (p≤0.001). The increase in the KAP and medication adherence scores from baselineto the follow‑up in the intervention group was found to be significantly higher than the control group. There was a reduction in the mean FBS frombaseline to the follow‑up in both the groups but a statistically significant higher reduction in the mean FBS was found in the intervention group frombaseline to the final follow‑up when compared to the control group (p < 0.001).Conclusion: A better KAP of diabetic patients about their disease can improve the medication adherence behavior which in turn can improve clinicaloutcomes. The patient education should be a continuous process, and patients should be assessed at every subsequent visit for medication adherenceto achieve better health outcome.Keywords: Diabetes, Adherence, Knowledge, attitude and practices, Patient education

Incidence of Adverse Drug Reactions in Patients on Cancer Chemotherapy in a Tertiary Care Teaching Hospital

ABSTRACT To assess the incidence of ADRs and their causal relationship to chemotherapeutic agents and to evaluate the severity and preventability of the ADRs. Patients above 18 years of age, on cancer chemotherapy were included. ADRs experienced by patients were identified and categorized using National Cancer Institute Common Terminology Criteria version 3.0 Questionnaire. The causality assessment of suspected ADRs was done using WHO and Naranjo's scales, severity assessment of ADRs using Hartwig and Siegel scale and preventability of ADRs using Schumock and Thornton scale. Results: The study was conducted in 109 patients (46 males, 63 females; mean age 53.75±12.75 years). Majority of the patients had breast cancer. Dry mouth and taste disturbances, were major ADRs found in 82.50% patients, dermatological ADRs alopecia, eczema and acne in 68.80%, hematological ADRs in 52.20%, and the least were the constitutional symptoms and renal ADRs (9.10% each). Causality assessment of ADRs using WHO scale identified 70.50% ADRs as Possible, 25.9% as Probable and only 1 ADR had a "Certain" causal link with the drug. Naranjo scale identified 61.4% ADRs as Probable, 36.6% as Possible and only one ADR had a "Definite" causal link with the drug. Severity assessment showed 65.90% as mild, 34.86% as moderate and none as severe ADRs. Nausea, vomiting, anorexia, fever, decrease in hemoglobin and neutrophil count were definitely preventable, diarrhea and constipation were probably preventable and the rest were not preventable. By implementing the ADR monitoring and reporting system, safe use of medications can be achieved

Studies on the synthesis of the toxins, pardaxin, δ-toxin and their analogues by solid-phase methods

Studies in our laboratory have been directed towards understanding the mechanism of action of two hydrophobic toxins, pardaxin comprising 33 residues and δ-toxin comprising 26 residues. Since isolation of these peptides in large amounts from natural sources is not convenient, we have explored synthetic approaches to get these peptides as well as their analogs. We have used chemistry specific to fluorenylmethoxycarbonyl (Fmoc) andt-butyloxycarbonyl (Boc) amino acids. Synthesis specific for Fmoc amino acids was carried out manually as well as on a semi-automated continuous flow peptide synthesizer. Synthesis specific for Boc amino acids was carried out manually. The protocols used by us have yielded 15-33 residue peptides which are of high purity. Even in peptides where heterogeneity was present, pure peptide could be obtained in good yields using simple gradients in fast performance liquid chromatography. The synthesis of pardaxin, δ-toxin and several analogs should help in identifying the molecular determinants of biological activity

Ethyl 2-(7-oxo-3,5-diphenyl-1,4-diaze­pan-2-yl)acetate

In the title compound, C21H24N2O3, the diazepane ring adopts a chair conformation. The central diazepane ring forms dihedral angles 67.80 (7) and 72.29 (5)° with the two benzene rings. The eth­oxy­carbonyl group is disordered over two conformations with site-occupancy factors of 0.643 (5) and 0.357 (5). In the crystal, inversion dimers linked by pairs of N—H⋯O hydrogen bonds generate R 2 2(8) loops

Evaluation of an Antimicrobial L-Amino Acid Oxidase and Peptide Derivatives from Bothropoides mattogrosensis Pitviper Venom

Healthcare-associated infections (HAIs) are causes of mortality and morbidity worldwide. The prevalence of bacterial resistance to common antibiotics has increased in recent years, highlighting the need to develop novel alternatives for controlling these pathogens. Pitviper venoms are composed of a multifaceted mixture of peptides, proteins and inorganic components. L-amino oxidase (LAO) is a multifunctional enzyme that is able to develop different activities including antibacterial activity. In this study a novel LAO from Bothrops mattogrosensis (BmLAO) was isolated and biochemically characterized. Partial enzyme sequence showed full identity to Bothrops pauloensis LAO. Moreover, LAO here isolated showed remarkable antibacterial activity against Gram-positive and -negative bacteria, clearly suggesting a secondary protective function. Otherwise, no cytotoxic activities against macrophages and erythrocytes were observed. Finally, some LAO fragments (BmLAO-f1, BmLAO-f2 and BmLAO-f3) were synthesized and further evaluated, also showing enhanced antimicrobial activity. Peptide fragments, which are the key residues involved in antimicrobial activity, were also structurally studied by using theoretical models. The fragments reported here may be promising candidates in the rational design of new antibiotics that could be used to control resistant microorganisms

Crystal structure and Hirshfeld surface analysis of two imidazo[1,2-a]pyridine derivatives: N-tert-butyl-2-(4-methoxyphenyl)-5-methylimidazo[1,2-a]pyridin-3-amine and N-tert-butyl-2-[4-(dimethylamino)phenyl]imidazo[1,2-a]pyridin-3-amine

In the title imidazo[1,2-a]pyridine derivatives, N-tert-butyl-2-(4-methoxyphenyl)-5-methylimidazo[1,2-a]pyridin-3-amine, C19H23N3O, (I), and N-tert-butyl-2-[4-(dimethylamino)phenyl]imidazo[1,2-a]pyridin-3-amine, C19H24N4, (II), the 4-methoxyphenyl ring in (I) and the 4-(dimethylamino)phenyl ring in (II) are inclined to the respective imidazole rings by 26.69 (9) and 31.35 (10)°. In the crystal of (I), molecules are linked by N—H...N hydrogen bonds, forming chains propagating along the [001] direction. The chains are linked by C—H...π interactions, forming layers parallel to the (010) plane. In (II), the crystal packing also features N—H...N hydrogen bonds, which together with C—H...N hydrogen bonds link molecules to form chains propagating along the c-axis direction. The chains are linked by C—H...π interactions to form layers parallel to the (100) plane. Inversion-related layers are linked by offset π–π interactions [intercentroid distance = 3.577 (1) Å]. The intermolecular interactions of both compounds were analyzed using Hirshfeld surface analysis and two-dimensional fingerprint plots

A study of drug-drug interactions in cancer patients of a south Indian tertiary care teaching hospital

Background : Drug interactions in oncology are of particular importance owing to the narrow therapeutic index and the inherent toxicity of anticancer agents. Interactions with other medications can cause small change in pharmacokinetics or pharmacodynamics of chemotherapeutic agents that could significantly alter their safety and efficacy. Aim : To identify and document the potential drug-drug interactions in prescriptions of patients receiving cancer chemotherapy. Settings and Design : A tertiary care teaching hospital based prospective study. Materials and Methods : Patients admitted in the medical oncology wards with different types of malignancies and receiving cancer chemotherapy during the period of June 2009 to November 2009 were included in the study. A detailed data collection was done in a specially designed proforma with ethical approval and consent of patients and their prescriptions were subjected to drug-drug interaction screening using Drug Interaction Fact Software Version-4 and standard references. Incidence of drug-drug interactions, their types, correlation between age, cancer type, number of drugs prescribed and incidence of drug interactions were analyzed. Statistical Analysis : Logistic regression analysis and Odds ratio were performed to identify the incidence of drug-drug interactions and their correlation with the factors above mentioned. Results : A total of 75 patients (32 males and 43 females; median age 56 years, age range 23-74) were enrolled in the study and their prescriptions were screened. 213 interactions were identified of which, 21 were major, 121 were moderate and 71 were minor. There were 13 (6.1%) clinically significant interactions between anticancer drugs and 14 (6.5%) drug-drug interactions between anticancer drugs and other drugs prescribed for co-morbidities. There was a positive correlation between number of drugs prescribed and drug interactions (P=0.011; OR 0.903). Conclusion : Though there was not any life threatening interactions, the potential interactions were brought to the oncologist purview for ensuring patients safety and to avoid undesirable effects