JOURNAL OF ASIAN ASSOCIATION OF SCHOOLS OF PHARMACY - Volume 11, January - December 2022

Pages: 6-14

Date of Publication: 25-Oct-2022

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Molecular modelling studies of some furo[2,3-d]pyrimidines and pyrrolo[2,3-d]pyrimidines as multiple receptor tyrosine kinase inhibitors

Author: Faridah Olubunmi Shuaib, Malina Jasamai, Kabir Abdu

Category: Pharmacy

Abstract:

Tyrosine kinases (TKs) have been implicated in causing tumour growth, angiogenesis and metastasis. Multiple receptor tyrosine kinase (RTK) inhibitors in clinical use have been reported to have adverse effects on hair and skin, hence this makes it impetus to discover new anticancer agents with milder side effects. Furopyrimidines and pyrrolopyrimidines have been reported to exhibit diverse pharmacological properties including TK inhibition. In this study, molecular modelling studies and in silico evaluation of pharmacokinetics as well as physicochemical properties were conducted on the furopyrimidines and pyrrolopyrimidines using PyRx-virtual screening tool, Molinspiration and DataWarrior software respectively. The docked compounds exhibited good binding affinity energies and anchored well inside the binding pockets of all the TK receptors used in our study. The predicted pharmacokinetic and physicochemical properties of the compounds showed that they violated one Lipinski’s rule of five each and displayed no toxicity potential (mutagenic and tumorigenic), hence this suggests they could pose as potential tyrosine kinases inhibitors candidates with milder side effects.

Keywords: tyrosine kinase inhibitors, furo-pyrimidines, pyrrolo-pyrimidines, molecular modelling