Aryloxy Alkyl Theophylline Derivatives As Antifungal Agents: Design, Synthesis, Biological Evaluation and Computational Studies

Infectious diseases are still one of the leading causes of death and disability in human society. Synthetic antimicrobial agents have recently emerged as promising candidates against drug-resistant pathogens. Here we described an efficient procedure for synthesis of aryloxyalkyl theophylline analouges as novel antimicrobial agents. Fourtheen new compounds were synthesized (5 a-5 n) and their chemical structures were approved by different spectroscopic methods. The synthesized compounds were screened for their antimicrobial activities by broth micro dilution method as recommended by Clinical and Laboratory Standards Institute (CLSI). Molecular docking studies were also performed to forecast their binding modes against cytochrome P-450 lanosterol 14 alpha-demethylase as a main target. The results represented appropriate correlation between molecular docking and antimicrobial activity of the compounds. Based on biological results and in silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions, compound 5 g can be considered as an ideal antimicrobial agent for the future studies.