Synthesis, Structural Investigation, Antiphospholipases, Antiproteases and Antimicrobial Activities of 2-(4-hydroxy-3-methoxy-benzylidene)-6-methoxy-3,4-dihydro-2H-naphthalen-1-one and 4 (4 hydroxy-3-methoxy-phenyl)-8-methoxy-3,4,5,6-tetrahydro-1H-benzo[h]quinazoline-2-thione

The molecular structure aspects of 2-(4-hydroxy-3-methoxy-benzylidene) -6-methoxy-3,4-dihydro-2H-naphthalen-1-one 3 and 4 (4 hydroxy-3-methoxy-phenyl)- 8-methoxy-3,4,5,6-tetrahydro-1H-benzo[h]quinazoline-2-thione 5 were investigated using spectroscopic analyses and DFT calculations. The calculated geometric parameters of the most stable isomer of 3 were in good agreement with the experimental data obtained from its X-ray analysis. On the basis of the HOMO and LUMO energies different reactivity descriptors such as chemical potential (μ), hardness (η), softness (S) and the electrophilicity index (ω) were calculated. It was found that the electrophilicity index (ω) of 3 is higher than that for 5 and the electronic chemical potential of 5 is higher than 3. Also the hardness is lower for 3 than 5 which has larger number of electronegative atoms. The calculated 13C and 1H NMR chemical shifts at the optimized geometry of the studied compounds were correlated well with the experimental data and showed high correlation coefficients (R2). Both molecules were screened against some selected proteases, phospholipases, bacterial and fungal strains. Compound 3 demonstrated better antiproteases activity than 5 with its maximum inhibitory activity against trypsin. Interestingly, while 3 demonstrated moderate inhibition against all tested phospholipases, compound 5 was more potent in inhibiting the catalytic activities of DrG IB and SG IBsPLA2s than oleanolic acid the reference antiphospholipase. Therefore, compound 5 may serve as a potential candidate for further development to identify therapeutic agents for treatment of diet induced obesity and diabetes. Antibacterial screening revealed that while 5 was completely inactive, 3 demonstrated promising inhibitory potential against some microbes with the lowest IC50 value against gram negative Klebsiella pneumoniae ATCC 700603.

Nahed N. E. El-Sayed, Norah M. Almaneai, Saied M. Soliman, Abir Ben Bacha and Hazem A. Ghabbour