Synthesis, druglikeness and electro-optical parameters estimation of some monoterpenic ester derivatives of theophylline7-acetic acid

personАвтори: Al. Zlatkov, B. Zlatkov, L. Andonova, M. Georgieva, S. Pankova, Y. Koleva


A series of monoterpenic ester derivatives of theophylline 7-acetic acid with a chosen monoterpene alcohol were synthesized, according to two synthetic pathways. The structure of the new products was elucidated with TLC characteristics, IR and 1H-NMR spectra. By evaluation of some electro-optical parameters of the studied compounds was established, that the hydrophilicity and the values of HOMO/LUMO energies are of great importance for the biological activity. An elucidation of their drug likeness was made, based on Lipinski’s Rule of Five parameters. It was determined, that the newly synthesized products are in good agreement with Lipinski’s Rule of Five limitations, which is a premise for good pharmacokinetics. This was also conformed from the results for the %ABS parameter, whereas the target compounds are with commensurable %ABS.

The possible enzymatic activity of the newly obtained products was determined. It was found, that compound 3c expresses good enzyme inhibitory activity comparable to the one obtained for the already published product 3a. The obtained values showed that both products are 2-4 times more active, than the initial compound. Using PBT profiler web server, the potential persistence, bioaccumulation and toxicity for the newly synthesized compounds was determined, as part of the EPA criteria. It was concluded that the target structures are not PBT, whereas the synthesized derivatives are persistent, do not bioaccumulate and are toxic, where the least toxic products are 3b,c.

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