Personne :
Zarifi Khosroshahi, Mitra

Photo de profil
Adresse électronique
Date de naissance
Projets de recherche
Structures organisationnelles
Fonction
Nom de famille
Zarifi Khosroshahi
Prénom
Mitra
Affiliation
Université Laval. Faculté de pharmacie
ISNI
ORCID
Identifiant Canadiana
ncf11930132
person.page.name

Filtres

2018 - 20192
Réinitialiser les filtres

Paramètres

Auteur: Fortin, Sébastien ×

Résultats de recherche

Voici les éléments 1 - 2 sur 2
  • Publication
    Accès libre
    Evaluation of the time-dependent antiproliferative activity and liver microsome stability of 3 phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzenesulfonates as promising CYP1A1-dependent antimicrotubule prodrugs
    (Pharmaceutical Press, 2019-11-14) Zarifi Khosroshahi, Mitra; Fortin, Sébastien; Gobeil, Stéphane; Gaudreault, René C.; Gagné-Boulet, Mathieu; Chavez Alvarez, Atziri Corin
    Objectives In this study, the antiproliferative activity of 3 phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs) was assessed in a time-dependent manner together with their hepatic stability and metabolism using human, mouse and rat liver microsomes. Methods CEU-818, -820 and -913 were selected as promising hit compounds. Their antiproliferative activity on human breast carcinoma MCF-7 cells was evaluated using escalating concentrations of drugs at 24, 36 and 48 h and the sulforhodamine B assay. Their hepatic stability was evaluated by HPLC-UV of extracts obtained from human, mouse and rat liver microsomes. Key findings The antiproliferative activity of PAIB-SOs is concentration and time-dependent and requires between 24 and 36 h of contact with MCF-7 cells to detect a significant antiproliferative activity. PAIB-SOs stability in microsomes usually decreases following this order: human ≈ (rat > mouse). The CEU-913 exhibits the longest half-life in rat and human liver microsomes while the CEU-820 exhibits the longest half-life in mouse liver microsomes. Conclusions Our in vitro results suggest that PAIB-SOs should have a minimum contact time of 24 h with the tumour to trigger significant antitumoural activity. The activity of mouse liver microsomes towards PAIB-SOs is higher than rat microsomes and tends to be higher than human liver microsomes.
  • Publication
    Accès libre
    4-(3-Alkyl-2-oxoimidazolidin-1-yl)-N-phenylbenzenesulfonamides as new antimitotic prodrugs activated by cytochrome P450 1A1 in breast cancer cells
    (Elsevier, 2018-09-04) Chavez Alvarez, Atziri Corin; Zarifi Khosroshahi, Mitra; Fortin, Sébastien; Côté, Marie-France; Gagné-Boulet, Mathieu
    The role and the importance of the sulfonate moiety in phenyl 4-(2-oxo-3-alkylimidazolidin-1-yl)benzenesulfonates (PAIB-SOs) were assessed using its bioisosteric sulfonamide equivalent leading to new cytochrome P450 1A1 (CYP1A1)-activated prodrugs designated as 4-(3-alkyl-2-oxoimidazolidin-1-yl)-N-phenylbenzenesulfonamides (PAIB-SAs). PAIB-SAs are active in the submicromolar to low micromolar range showing selectivity toward CYP1A1-expressing MCF7 cells as compared to cells devoid of CYP1A1 activity such as MDA-MB-231 and HaCaT cells. The most potent, PAIB-SA 13, bearing a trimethoxyphenyl group on ring B blocks the cell cycle progression in G2/M phase, disrupts the microtubule dynamics and is biotransformed by CYP1A1 into CEU-638, its potent antimicrotuble counterpart. Structure-activity relationships related to PAIB-SOs and PAIB-SAs evidenced that PAIB-SOs and PAIB-SAs are true bioisosteric equivalents fully and selectively activatable by CYP1A-expressing cells into potent antimitotics.