Synthesis, molecular docking and biological evaluation of bis-pyrimidine Schiff base derivatives

Background: Heterocyclic pyrimidine nucleus, which is an essential base component of the genetic material of deoxyribonucleic acid, demonstrated various biological activities. A series of bis-pyrimidine Schiff bases were synthesized and screened for its antimicrobial and anticancer potentials. The molecular docking study was carried to find the interaction between active molecules with receptor. Results: The structures of synthesized bis-pyrimidine Schiff bases were confirmed by spectral studies. The synthesized bis-pyrimidine derivatives were evaluated for their antimicrobial activity (MIC = μmol/mL) against selected Gram positive; Gram negative bacterial and fungal strains by tube dilution method. The anticancer activity (IC₅₀ = μmol/mL) of the synthesized compounds was determined against human colorectal carcinoma (HCT116) cancer cell line by Sulforhodamine B (SRB) assay. Molecular docking studies provided information regarding the binding mode of active bis-pyrimidine Schiff bases with the cyclin-dependent kinase 8 (CDK8) receptor. Conclusions: The antimicrobial screening results indicated that compounds, q1 (MIC_bs = 0.83 μmol/mL), q16 (MIC_an = 1.54 μmol/mL and MIC_ec = 0.77 μmol/mL), q1 and q19 (MIC_ca = 0.41 μmol/mL) and q20 (MIC = 0.36 μmol/mL) are the most active ones. Compounds q1 (IC₅₀ = 0.18 μmol/mL) have emerged as potent anticancer molecule against human colorectal carcinoma cancer cell line than the reference drug, 5-fluorouracil. Molecular docking studies indicated that compound q1 (the most active molecule) has the maximum hydrogen bond interaction (four) and π-π stacking (three) network among the bis-pyrimidine Schiff bases. [Figure not available: see fulltext. Caption: Graphical illustration of predicted binding mode of bis-pyrimidine Schiff bases in the active site of CDK8. a. Compound 1 (magenta color), b. Compound 5 (green color), c. Compound 8 (red color), d. Compound 13 (split pea color).]