PhD Scientific Days 2024

Poster Session R - Pharmaceutical Sciences and Health Technologies 2.

Characterization of opioid agonist morphine derivatives with emphasis on medicinal chemistry

Előadó neve

Ms. Malik, Alaa

Neptun code

D0K8FR

Előadó munkahelye

Semmelweis University

Előadó telefonszáma

0036704016428

Előadó e-mail címe

alaa.malik@phd.semmelweis.hu

Az előadás címe

Characterization of opioid agonist morphine derivatives with emphasis on medicinal chemistry

Szerző(k) neve és munkahelye

Alaa Malik¹, Béla Noszál¹, Károly Mazák¹

1: Semmelweis University

Bemutatás módja

Poszter

Szekció

Poster Session R - Pharmaceutical Sciences and Health Technologies 2.

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction: Relieving of severe pains is an unmet medical need, in which the derivatives of morphine are of prime importance. A thorough understanding of physicochemical properties are crucial to develop new compounds of improved therapeutic properties.

Aim:This study quantifies basicity, lipophilicity and permeability, the biorelevant physicochemical parameters of thirty opioid agonists, including eleven newly synthesized compounds.

Methods: pH-potentiometry and shake-flask method were used to determine species-specific basicity and lipophilicity. Permeability was measured through a brain-specific parallel artificial membrane to predict BBB penetration.

Results: O-methylation in position 3, isomerization in position 6, saturation of the 7,8 double bond, 14-hydroxylation, and the substitution of N-(β-phenylethyl) and N-cyclobutylmethyl side chains all influence these physicochemical properties, which can be interpreted by electron-withdrawing and -sending, hydrogen bonding and solvation effects. 14-hydroxylation, and hydrogen bonding with the tertiary amino group effect remarkably these parameters and can not be assessed by currently available computational predictions. Oxidation of the 6-hydroxyl group and replacement of the N-methyl group with the N-(β-phenylethyl) group also result in significant changes in electron-distribution and the concomitant binding propensities, that in silico programs fail to predict.

Conclusion:
The quantified species-specific charge, charge-distribution and lipofilicity values provide sound means to interpret subtle electronic effects, contributing to the development of more effective pain-relieving drugs.

Funding:
Stipendium Hungaricum scholarship

University

Semmelweis University

Supervisor

prof.Béla Noszál

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

7990

Start

16:30

End

16:33