Innovational combination of hetero-bifunctional N-PEG quinoline scaffolds derivatives with improved anticancer activity against breast and colon cancer cell lines and P-glycoprotein, cytochrome p450 enzyme activity prediction.

Mahesh Gaidhane,Kushal Lanjewar,Ajay Ghatole,Kishor Hatzade

doi:10.3906/kim-2006-13

Abstract

Polyethylene glycol (PEG) is a polymer that is widely used as a carrier for drug delivery systems (DDS). A library of N-PEGylated quinoline derivatives of PEG molecular weight 200 was prepared rapidly after the activation of PEGs using maleic anhydride. Quinoline with a polymer backbone is essential as new material. PEG is a water-soluble nonionic polymer approved by food and drug organizations for medicine applications. Because of its nontoxic grapheme, it is widely utilized in numerous biochemical, cosmetic, pharmaceutical, and industrialized applications. The modern SwissADME is a web tool that stretches free admittance to a pool of hasty, yet solid, clarifying models for physicochemical properties, pharmacokinetics, and therapeutic science. The present facile synthetic strategy can be a practical approach for incorporating polymeric carriers conjugated with drug moieties, either in the backbone of the polymer or as a terminal and pendant group on the polymer chains.

Highlights

A library of N-polyethylene glycol(PEG)ylated quinoline derivatives of Polyethylene glycol (PEG) molecular weight 200 was prepared rapidly after the activation of PEGs using maleic anhydrides
Result and discussion An extension of PEG-supported chemistry was linked in the arena of functionalized polymers as reagent supports
The PEGylation chemistry successfully demonstrated at the amino group was situated at C-7 of the quinoline hybrids

Summary

Introduction

A library of N-polyethylene glycol(PEG)ylated quinoline derivatives of PEG molecular weight 200 was prepared rapidly after the activation of PEGs using maleic anhydrides. Prepared was novel PEG N-terminal quinoline substituted derivatives and it was shown that, when related to a heterogeneous commercially-existing counterpart, they held promising reaction kinetics equal to the Staudinger and Mitsunobu etherification reactions They were evaluated for their in vitro anticancer, antibacterial, and antifungal activities. It was opted to activate the PEG by turning it to its acid derivative and coupling it with an amino group of quinoline molecules. The most useful for polypeptide modification is monoacid PEG, which has the general structure: HO-(CH2CH2O) n-CH2CH2-O-COOH For this monoacid derivative of PEG coupled to a 6-amino-2-chloroquinoline-3-carbonitrile (3a), it was necessary to activate the PEG by maleic anhydride. The TLC technique was used to check the purity of the compound using silica gel G

Biological assay

H CN N Cl

A2 B1 B2 D1 D2

Findings

Albicans