RESUMO
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.
Assuntos
COVID-19 , Preparações Farmacêuticas , Farmácia , Estudantes de Farmácia , Humanos , Pandemias , SARS-CoV-2RESUMO
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.
Assuntos
Antineoplásicos , Triterpenos , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Triterpenos Pentacíclicos , Relação Estrutura-Atividade , Triterpenos/síntese química , Triterpenos/química , Triterpenos/farmacologia , Ácido Betulínico , Ácido UrsólicoRESUMO
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.
Assuntos
Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Ácido Oleanólico/análogos & derivados , HIV-1/efeitos dos fármacos , Células HT29 , Humanos , Estrutura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Triterpenos Pentacíclicos , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos , Ácido Betulínico , Ácido UrsólicoRESUMO
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.
Assuntos
Relação Quantitativa Estrutura-Atividade , Receptores de Serotonina/efeitos dos fármacos , Agonistas do Receptor de Serotonina/química , Agonistas do Receptor de Serotonina/farmacologia , Simulação por Computador , Cristalografia por Raios X , Modelos Moleculares , Conformação Molecular , Receptores 5-HT3 de SerotoninaRESUMO
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.
Assuntos
Receptores de Serotonina/efeitos dos fármacos , Antagonistas da Serotonina/síntese química , Agonistas do Receptor de Serotonina/síntese química , Animais , Colo/efeitos dos fármacos , Colo/fisiologia , Relação Dose-Resposta a Droga , Cobaias , Técnicas In Vitro , Modelos Moleculares , Receptores 5-HT3 de Serotonina , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Relação Estrutura-AtividadeRESUMO
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.