Acta Pharmaceutica, Vol. 67 No. 3, 2017.
Original scientific paper
https://doi.org/10.1515/acph-2017-0026
Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds
MIYASE GÖZDE GÜNDÜZ
; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey
GAETANO RAGNO
; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy
RAHIME ŞIMŞEK
; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey
MICHELE DE LUCA
; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy
CIHAT ŞAFAK
; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey
FEDORA GRANDE
; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy
AHMED EL-KHOULY
; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey
FATMA İŞLI
; Department of Pharmacology, Faculty of Medicine, Gazi University, 06560, Ankara, Turkey
ŞENIZ YILDIRIM
; Department of Pharmacology, Faculty of Medicine, Gazi University, 06560, Ankara, Turkey
GÖKÇE SEVIM ÖZTÜRK FINCAN
; Department of Pharmacology, Faculty of Medicine, Gazi University, 06560, Ankara, Turkey
GIUSEPPINA IOELE
; Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy
Abstract
This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs) endowed with good muscle relaxant activity and stability to light. Six new condensed DHPs were synthesized by the microwave irradiation method. A long-chain ester moiety [2-(methacryloyloxy)ethyl] and various substituents on the phenyl ring were demonstrated to affect the muscle relaxant activity occurring in isolated rabbit gastric fundus smooth muscle strips. Forced photodegradation conditions were applied to the molecules according to the ICH rules. The degradation profile of the drugs was monitored by spectrophotometry coupled with the multivariate curve resolution technique. Formation of the oxidized pyridine derivative was observed for all the studied DHPs, except for one compound, which showed very fast degradation and formation of a second photoproduct. Pharmacological tests on the molecules showed a good muscle relaxing effect, with a mechanism similar to that of nifedipine, however, proving to be more stable to light.
Keywords
1,4-dihydropyridine compounds; muscle relaxant; drug design; structure activity relationship; photostability; MCR analysis
Hrčak ID:
181338
URI
Publication date:
30.9.2017.
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