PhD Scientific Days 2025

Pharmaceutical Sciences and Health Technologies I.

Biorelevant Physicochemical Characterization of Morphine Derivatives to Improve Analgesic Selectivity

Előadó neve

Malik Alaa, PhD

Neptun code

D0K8FR

Előadó munkahelye

Semmelweis University

Előadó telefonszáma

0036704016428

Előadó e-mail címe

alaa.malik@phd.semmelweis.hu

Az előadás címe

Biorelevant Physicochemical Characterization of Morphine Derivatives to Improve Analgesic Selectivity

Szerző(k) neve és munkahelye

Alaa Malik¹, Prof. Noszál Béla¹, Dr. Mazák Károly¹

1: Semmelweis University, Department of Pharmaceutical Chemistry, Hőgyes E. u. 9., H-1092 Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Pharmaceutical Sciences and Health Technologies I.

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction:
Relieving severe pains is an unmet medical need, in which opioids are of prime importance and in the focus of pharmaceutical companies. New derivatives of morphine are systematically synthesized with the aim of separating the advantageous therapeutic properties from the addictive aspects of morphine.

Aims:
The objective of this study is to characterize the physicochemical properties, namely basicity, lipophilicity and permeability of thirty opioid ligands, which include eleven newly synthesized compounds.

Methods:
pH-potentiometry and the shake-flask method were used for the characterization of species-specific basicity and lipophilicity. The effective permeability was determined using a brain-specific parallel artificial membrane permeability assay.

Results:
Structural modifications, namely O-methylation in position 3, isomerization in position 6, saturation of the double bond in position 7, 14-hydroxylation, and the substitution of N-(β-phenylethyl) and N-cyclobutylmethyl side chains all have various effects on these physicochemical properties, and these are explained and compared to computationally predicted values. Computational predictions inadequately capture hydrogen bond formation with the tertiary amino group in case of 14-hydroxylation, just as the effects of hydroxy oxidation at position 6 and N-methyl substitution with N-(β-phenylethyl).

Conclusion:
The relationship between lipophilicity, permeability and potency is presented by lipophilic efficiency plots that reveal the most promising compounds. This study emphasizes the importance of experimental determination of these essential physicochemical parameters, furthermore, it can contribute to a more thorough understanding of the pharmacokinetic properties.

Funding:
This research was funded by the Stipendium Hungaricum scholarship.

Email: alaa.malik@phd.semmelweis.hu
University: Semmelweis University, Department of Pharmaceutical Chemistry, Budapest, Hungary
Supervisor: Prof. Béla Noszál

University

Semmelweis University

Supervisor

Prof. Noszál Béla

Publication of my abstract

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

phd.section.field

in doctoral studies before complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

jóváhagyta

Előadó

7990

Start

14:30

End

14:45