No abstract

Background: Prostate cancer is one of the leading causes of death. Though many drugs are being used as effective anticancer agents resistance and side effects necessitates development of target selective and safe anticancer agents. Objectives: The objectives of our work were to identify the important pharmacophoric features and correlate structure of Trifluoro substituted pyrimidine and predict their anticancer activity using QSAR, pharmacophore modelling, and docking studies. Materials and Methods: In this research investigation molecular modelling approach was adopted to develop efficacious Trifluoro substituted pyrimidine derivatives as anticancer agents. Results: Statistically significant models were generated using 2D-MLR method (correlation coefficient (r 2 ) of 0.9207 and a significant Leave-one-out cross-validated correlation coefficient (q 2 ) of 0.8187) and 3D QSAR studies by SA-kNN method (q 2 = 0.723). 2D QSAR models indicated the important of SssNHcount and H-bond acceptor groups to augment the activity. Similarly, 3D QSAR results indicated the requirement of less electronegative and less steric substituents. Essential features such as aromatic and hydrogen bond acceptor features of compounds to interact with the target were highlighted using pharmacophore mapping. These studies prompted us to design new molecules using lead grow tool. Designed compounds were screened for their drug likeness, activity and toxicity using SWISS ADME, Osiris and PASS respectively. Finally docking and binding affinities of designed molecules were studied on EGFR 1M17. Conclusion: Thus, these studies collectively have helped to establish relationship between pyrimidine nucleus and anticancer activity.

Pyrimidine and Triazine are rewarding pharmacophores as seen from their presence in different naturally and synthetically occurring drug molecules. Hybridization is a functional concept used in drug design. This updated review encompasses various synthetic routes, procedures that have been used to prepare molecular hybrids of Pyrimidine and Triazine, detailed structure-activity relationship, and molecular docking studies with patents granted. The most potent and promising hybrid compounds have also been identified. The study has revealed the synthetic feasibility of Pyrimidine- Triazine hybrids along with a plethora of potent biological activities such as Anticonvulsant, Antiviral, Anti-inflammatory, Analgesics, etc. This paper highlights the importance of coupling Pyrimidine and Triazine to provide better insight for medicinal chemists to further explore the hybrid for significant therapeutic effect.