Synthesis, docking and antimicrobials evaluation of novel pyrazolotriazines as RNA polymerase inhibitors
: A series of novel pyrazolo[1,5-a][1,3,5]triazine and pyrazolo[5,1-c][1,2,4]triazine, were synthesized from the 5-aminopyrazoles 3, which was previously prepared and considered a starting precursor for synthesizing many promising bioactive compounds. Thus, all the prepared compounds were evaluated as antimicrobial agents. Also, the minimum inhibitory concentration (MIC) for the most potent compounds was measured. Moreover, docking studies were performed using the newly prepared compounds to evaluate their affinity to different bacterial target proteins with varying modes of action involving cell wall inhibition, protein and nucleic acid synthesis, and antimetabolites. Some of the prepared compounds revealed potent activity towards some of the bacterial and fungal strains used. After molecular docking study validation, it seemed that the synthetic compound mode of action was through RNA synthesis inhibition, while the DNA-dependant RNA polymerase beta subunit repC (PDB: 2AUK) was the probable protein target. The RNA polymerase inhibitory activity was measured for the most potent antimicrobial compounds with high docking scores for more evidence.