Pharmacological classification and activity evaluation of furan and thiophene amide derivatives applying semi-empirical ab initio molecular modeling methods.

Leszek Bober,Piotr Kawczak,Tomasz Baczek

doi:10.3390/ijms13066665

Abstract

Pharmacological and physicochemical classification of the furan and thiophene amide derivatives by multiple regression analysis and partial least square (PLS) based on semi-empirical ab initio molecular modeling studies and high-performance liquid chromatography (HPLC) retention data is proposed. Structural parameters obtained from the PCM (Polarizable Continuum Model) method and the literature values of biological activity (antiproliferative for the A431 cells) expressed as LD50 of the examined furan and thiophene derivatives was used to search for relationships. It was tested how variable molecular modeling conditions considered together, with or without HPLC retention data, allow evaluation of the structural recognition of furan and thiophene derivatives with respect to their pharmacological properties.

Highlights

The process of searching for anticancer drugs involves consideration of different structures with different mechanisms of action
The authors studied the biological activity, the antiproliferative effect of the A431 cells expressed as LD50, and conducted a preliminary assessment of the statistical relationship between biological activity and lipophilicity arriving at a higher consistency for derivatives of thiophene and the calculated lipophilicity parameters
The numerical values of all 10 structural parameters derived from the quantum-chemical calculations in vacuo with the use of the 6–31G (d, p) method for all 12 examined compounds are presented in

Summary

Introduction

The process of searching for anticancer drugs involves consideration of different structures with different mechanisms of action. The methods of searching for the optimal structures (drug design, combinatorial synthesis, screening, etc.) vary [1,2,3]. They established the retention factor, log k, as a measure of lipophilicity in isocratic conditions for the studied compounds along with the use of the classical Hansch method [5]. They calculated the logarithms of the partition coefficients, clog P, as an independent measure of lipophilicity. The authors studied the biological activity, the antiproliferative effect of the A431 cells expressed as LD50, and conducted a preliminary assessment of the statistical relationship between biological activity and lipophilicity arriving at a higher consistency for derivatives of thiophene and the calculated lipophilicity parameters (clog P)

Objectives

Methods

Results

Conclusion