ABSTRACT
OBJECTIVES: To characterize the engagement of students enrolled in the fifth year of pharmaceutical studies in the management of the health crisis due to the COVID-19 pandemic, and to identify some determinants of this engagement during this period. METHODS: With the health crisis, new missions have been entrusted during hospital internships, whereas certain internship sites were removed in hospitals and as part of the health service organization. In addition, some students who were no longer in internship returned to the hospital setting for helping in critical activities. Student engagement was studied with a questionnaire and focus groups including six or seven students in each group. RESULTS: Forty-three students participated to the study. The answers to the questionnaire highlighted that they were engaged, that they usually did not wait for compensation, and that most of them were satisfied by their activity during the crisis. The thematic analysis demonstrated that despite a feeling of frustration, which was often associated with the interruption of rewarded activities, and despite a stress due to the particular context, student engagement was supported by a better consideration of the pharmacist's role as a professional in public health and by a better acknowledgement of this role by other health professionals. CONCLUSION: This level of engagement is particularly encouraging because it is the witness of the ability of pharmacists to mobilize for general interest, even in adverse context.
Subject(s)
COVID-19 , Pharmaceutical Preparations , Pharmacy , Students, Pharmacy , Humans , Pandemics , SARS-CoV-2ABSTRACT
Fifteen new ursolic and betulinic triterpenoids, bearing various functionalities at C-3 and C-28 were synthesized as potential cytotoxic agents. All compounds were obtained by a hemisynthetic route via ursolic and betulinic acids. Preliminary screening of these compounds on human HT 29 colon cancer cells revealed inhibitory activity for three of them. Beta-D-Glucopyranosyl-3beta-hydroxyurs-12(13)-en-28-oate 1c, 3beta-3-(3-pyridyl)-prop-2-enoyloxyurs-12(13)-en-28-oic acid 1i and the potassium salt of 3beta-cinnamoyloxylup-20(29)-en-28-oic acid 2d demonstrated cytotoxic activity in the micromolar range: 8.0, 45.0 and 8.0 microM, respectively.
Subject(s)
Antineoplastic Agents , Triterpenes , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Survival/drug effects , Drug Screening Assays, Antitumor , HT29 Cells , Humans , Inhibitory Concentration 50 , Molecular Structure , Pentacyclic Triterpenes , Structure-Activity Relationship , Triterpenes/chemical synthesis , Triterpenes/chemistry , Triterpenes/pharmacology , Betulinic Acid , Ursolic AcidABSTRACT
The aim of this review is to update current knowledge on the betulinic, ursolic and echinocystic acids and their natural and semisynthetic analogs, focussing on their cytotoxic and anti-HIV activities. Then, the last results of the authors' team on unusual semisynthetic derivatives of these triterpenoids will be presented in order to establish structure/activity relationships.
Subject(s)
Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Oleanolic Acid/analogs & derivatives , HIV-1/drug effects , HT29 Cells , Humans , Molecular Structure , Oleanolic Acid/chemistry , Oleanolic Acid/pharmacology , Pentacyclic Triterpenes , Structure-Activity Relationship , Triterpenes/chemistry , Triterpenes/pharmacology , Tumor Cells, Cultured/drug effects , Betulinic Acid , Ursolic AcidABSTRACT
CATALYST and COMFA, two software packages for 3D QSAR studies, were associated to correlate the three-dimensional structures of 75 serotonin 5-HT3 ligands to their biological affinities. The conformational analysis and the influence of chemical function-based alignments (the basis of this association) on final results are discussed in this publication. These two analyses allow for precisely quantitating the weights of significant chemical groups or functions on the biological affinities.
Subject(s)
Quantitative Structure-Activity Relationship , Receptors, Serotonin/drug effects , Serotonin Receptor Agonists/chemistry , Serotonin Receptor Agonists/pharmacology , Computer Simulation , Crystallography, X-Ray , Models, Molecular , Molecular Conformation , Receptors, Serotonin, 5-HT3ABSTRACT
The design and synthesis of a new type of 5-HT3 ligand with subnanomolar affinity are described. The O-dialkylaminoethyloximinothienopyrrolizine structure was deduced from molecular modeling studies by replacement of an amidine moiety by an oximino one.
Subject(s)
Receptors, Serotonin/drug effects , Serotonin Antagonists/chemical synthesis , Serotonin Receptor Agonists/chemical synthesis , Animals , Colon/drug effects , Colon/physiology , Dose-Response Relationship, Drug , Guinea Pigs , In Vitro Techniques , Models, Molecular , Receptors, Serotonin, 5-HT3 , Serotonin Antagonists/pharmacology , Serotonin Receptor Agonists/pharmacology , Structure-Activity RelationshipABSTRACT
A definition of a partial agonists serotonin 5-HT3 pharmacophore was carried out by considering a three-dimensional model which correlates the chemical structures of series of piperazinopyrrolothienopyrazines, piperazinopyridopyrrolopyrazines, piperazinopyrroloquinolaxines, piperazinopyridopyrroloquinoxalines, aminoalkyloximinopyrroloindoles, aminoalkyloximinothienopyrrolizines, and aminoalkyloximinopyrrolizines with the biological affinities. The model is formed by five features corresponding to two hydrogen bond acceptors, one aromatic ring, one hydrophobic group, and one positive ionizable site (quaternary ammonium ions). The nature of the features and the distances between them explain the partial agonist activities of these compounds.
