Exploring of Chemical Profile and Biological Activities of Three Ocimum Species From Comoros Islands: A Combination of In Vitro and In Silico Insights.

Ocimum species have a great interest in different traditional medicinal systems. This study examined the chemical composition, antioxidant properties, enzyme inhibitory effects, and antibacterial and antifungal activities of the aerial parts of Ocimum gratissimum, Ocimum americanum, and Ocimum basilicum from the Comoros Islands. The extracts were analyzed using high-performance liquid chromatography-mass spectrometry (HPLC-MS) to determine their chemical composition.

Inhibition of secretory phospholipase A2. 1-design, synthesis and structure-activity relationship studies starting from 4-tetradecyloxybenzamidine to obtain specific inhibitors of group II sPLA2s.

Starting from 4-tetradecyloxybenzamidine (PMS815), a non-specific inhibitor of GI and GII PLA2s, we report in this work the discovery of the specificity through design, synthesis and structure-activity relationships studies of different kinds of PMS815 derivatives. The leading compound, 4,5-dihydro-3-(4-tetradecyloxybenzyl)-1,2,4-4H-oxadiazol-5-one (9b, PMS1062) exhibits a micromolar IC50 towards three group II PLA2s, while inactive towards four group I and one group III enzymes in two in vitro enzymatic assay conditions. It is also able to block the PLA2-II activities induced by LPS and IL-6 in HepG2 cell line and no cytotoxicity is observed when PMS1062 is tested up to a concentration of 100 microM in two different cell lines (A549 and LLC-PK1).

Inhibition of secretory phospholipase A2. 2-Synthesis and structure-activity relationship studies of 4,5-dihydro-3-(4-tetradecyloxybenzyl)-1,2,4-4H-oxadiazol-5-one (PMS1062) derivatives specific for group II enzyme.

We have recently reported the discovery of a series of specific inhibitors of human group IIA phospholipase A(2) (hGIIA PLA(2)) to display promising in vitro and in vivo properties. Here we describe the influence of different structural modifications on the specificity and potency against hGIIA PLA(2) versus porcine group IB PLA(2). The SAR results, as well as the logP and pK(a) values of oxadiazolone determined in this work, provide important information towards the comprehension of the mode of action of this kind of compounds.