Novel semisynthetic coumarin derivatives were synthesized to be developed as chemotherapeutic anticancer agents through topoisomerase II, VEGFR2 inhibition that leads to apoptotic cancer cell death. The coumarin amino acids and dipeptides derivatives were prepared by the reaction of coumarin-3-carboxylic acid with amino acid methyl esters following the N,N-dicyclohexylcarbodiimide (DCC) method and 1-hydroxy-benzotriazole (HOBt), as coupling reagents. The synthesized compounds were screened towards VEGFR2, and topoisomerase IIα proteins to highlight their binding affinities and virtual mechanism of binding. Interestingly, compounds 4k (Tyr) and 6c (β-Ala-L-Met) shared the activity towards the three proteins by forming the same interactions with the key amino acids, such as the co-crystallized ligands. Both compounds 4k and 6c exhibited potent cytotoxic activities against MCF-7 cells with IC₅₀ values of 4.98 and 5.85 µM, respectively causing cell death by 97.82 and 97.35%, respectively. Validating the molecular docking studies, both compounds demonstrated promising VEGFR-2 inhibition with IC₅₀ values of 23.6 and 34.2 µM, compared to Sorafenib (30 µM) and topoisomerase-II inhibition with IC₅₀ values of 4.1 and 8.6 µM compared to Doxorubicin (9.65 µM). Hence, these two promising compounds could be further tested as effective and selective target-oriented active agents against cancer.

The olive leaf extract and olive leaf indicated a high potential for application in food additives and foodstuffs. It could be these bio-products useful and important in condition therapy related with oxidative stress and can use it to develop functional foods and to improve the food's shelf life. The olive leaf chemical composition of Oleaeuropaea L. grown from eljouf in Saudi Arabia, using solvents of increasing polarity cyclohexane, dichloromethane, chloroform, ethyl acetate, methanol and ethanol was determined using by GC/MS. Furthermore, the antioxidant activity (diphenylpicrylhydrazyl (DPPH), anti-aging, and anti-tuberculosis of olive leaf extracts were evaluated. The results indicated that extract of Oleaeuropaea L. has a considerable contains in polyphenols (hydroxytyrosol, oleuropein and their derivatives) regarding its antioxidant effects, the major components were detected by GC/MS in Olea dichloromethane extract are Hexadecanoic acid (15.82%), 7(4Dimethylaminophenyl)3,3,12trimethyl3,12dihydro6 Hpyrano[2,3c]acridin 6 one (11.21%), and in Olea chloroform extract are Hexatriacontane (12.68%), nTetratr iacontane (10.95%). The results concluded that the plant extract of chloroform showed no anti-aging activities and the lower anti-aging activities for cyclohexane extract, while, the Olea dichloromethane extract was the most active extract. The obtained data confirmed that the most active extract of anti-tubercolisis was for chloroform and ethyl acetate extract, while, anti-tubercolisis activity of ethanolic extract was the lower. The extract amount as well as the solvent polarity influence the inhibitory activity. A favorable connection was demonstrated inter alia the leaf extracts antioxidant activity and the content of total phenol.

This study describes the synthesis of heterocyclic derivatives containing multiple nitrogen atoms serving as important moieties for developing novel antidiabetics through a simple synthetic pathway. We herein describe the synthesis and characterization of novel pyrimidine derivatives using one-pot reactions in a catalyst-free and efficient manner through a two-stage process involving the synthesis of 2-amino-4-hydrazinyl-6-methoxy pyrimidine, followed by a reaction with phenyl isothiocyanate derivatives. The structures of all the new compounds were confirmed via physical and spectral analysis. Furthermore, we evaluated the synthesized pyrimidine derivatives’ biological activities in relation to their potential roles as novel anti-diabetic agents by testing their activity profiles against the enzymes α-glucosidase and α-amylase. Compound 4 expressed the highest level of activity against α-glucosidase and α-amylase, with a greater inhibitory concentration (IC₅₀ of 12.16 ± 0.12 µM and IC₅₀ 11.13 ± 0.12 µM) compared to that of acarbose (IC₅₀ = 10.60 ± 0.17 µM and IC₅₀ = 11.30 ± 0.12 µM), which is widely used as a standard antidiabetic drug. The primary structure activity relationship analysis identified the impact of an electron- withdrawing group, especially with respect to fluorine on inhibitory activity. This was further confirmed in molecular docking studies, which demonstrated that both compounds exhibited similar inhibition patterns and emphasized the significance of incorporating a lipophilic electron-withdrawing substituent on the phenyl ring, along with the 2,4-diaminopyrimidine scaffold.