Design Synthesis and Evaluation of Some Novel Heterocyclic Compounds

Abstract

One of the very interesting heterocyclic moiety called Pyrido[2,3-d]pyrimidine, which are available in nature and exhibit a wide range of biological activities such as antifungal, antibacterial, antitumor, potent inhibitor of dihydrofolate reductase (DHFR), cyclin-dependent kinase 4 (CDK4) inhibitor, Tyrosine kinase inhibitor, antimalarial, anti-inflammatory and analgesic activity etc. These activities and information after detail literature survey are motivational for the synthesis of novel compounds of pyrido[2,3-d]pyrimidine. A simple and convenient method was used for the preparation of pyrido[2,3-d]pyrimidinecompounds. All the synthesized compounds were characterized by using FT-IR, 1H NMR and mass spectrometry. From the characterizations all the values of FTIR, 1H NMR and mass spectrum were found to be prominent. The novel pyrido[2,3-d]pyrimidine compounds(6a-r) were subjected to antibacterial screening of inhibitor and their determination of minimum inhibition concentration method (MIC) by broth micro-dilution methods using a cation-adjusted Mueller Hinton (MHII) mediumand single step resistance study. Growth inhibitory action of these novel pyrido[2,3-d]pyrimidinecompounds(7a-p) to evaluated for their CDK2/5 inhibition activity screened in vitro for their anti-proliferative activity was carried out on two cell lines, viz., colon cancer cell lines HCT116 and breast cancer cell lines MCF7 and their IC50 was calculated using GraphPad Prism version 5 for Windows. newlineThe various novel synthesized Pyrido[2,3-d]pyrimidine derivatives were found to exhibit potent antibacterial activity and cytotoxic activity comparable to standard one. The detailed synthesis, spectroscopic data, antimicrobial and cytotoxic activities of synthesized Pyrido[2,3-d]pyrimidine derivatives were reported. newlineFurther, in molecular designing and docking studies were performed on the Schrodinger modelling suite (Version 15.3), the compounds designed were subjected to energy minimisation by Ligprep module of the software.The crystal structure (PD