Utilising UPLC-QTOF-MS/MS to determine the phytochemical profile and in vitro cytotoxic potential of Ziziphora capitata L. with molecular docking simulation.

Ziziphora capitata (Lamiaceae family) aerial parts extract contains 57 metabolites, including flavonoids, phenolic acids, anthocyanins, and coumarins, as assessed by UPLC-QTOF-MS/MS. Successive extracts (hexane, chloroform, ethyl acetate, ethanol 95%, and water) were tested in vitro cytotoxic activity against HepG-2, MCF-7, HCT-116, A549, and PC3 cell lines. The results revealed that hexane extract exhibited the most potent cytotoxic activity among PC3 and A549 cell lines, IC50 = 47.1 ± 1.75 and 49.2 ± 1.08 µg/mL compared to Vinblastine IC50 = 42.47 ± 1.95 and 24.64 ± 1.18 µg/mL, respectively, and had a moderate impact on the remaining cell lines. Moreover, the chloroform and ethyl acetate extracts exhibited moderate affinity among all tested cell lines. Furthermore, the total phenolic and flavonoid contents were assessed. The molecular docking simulation was performed inside the effective sites of VEGFR-2 and TS as anticancer targets for the top ten phytochemicals. The results showed higher binding energy values for VEGFR-2 than for TS compared to vinblastine and co-crystallized ligands.

A new exploration toward adamantane derivatives as potential anti-MDR agents: Design, synthesis, antimicrobial, and radiosterilization activity as potential topoisomerase IV and DNA gyrase inhibitors.

Developing novel antimicrobial agents has become a necessitate due to the increasing rate of microbial resistance to antibiotics. All the newly adamantane derivatives were evaluated for their antimicrobial activities against six MDR clinical pathogenic isolates. The results exhibited that 13 compounds have from potent to good activity. Among those, five derivatives (6, 7, 9, 14a, and 14b) displayed the potent activities against the different isolates tested (MIC < 0.25 µg/ml with bacteria and <8 µg/ml with fungi) compared with Ciprofloxacin (CIP) and Fluconazole (FCA). Additionally, the potent adamantanes showed bactericidal and fungicidal effects based on (MBCs and MFCs) and the time-kill assay. The most active adamantane derivatives 7 and 14b exhibited a synergistic effect of ΣFIC ≤ 0.5 with CIP and FCA against the bacterial and fungal isolates. Moreover, no antagonistic effect appeared for the tested derivatives. Additionally, the interaction of DNA gyrase and topoisomerase IV enzymes with the compounds 6, 7, 9, 14a, and 14b exhibited potent antimicrobial activity using in vitro biochemical assays and gel-based DNA-supercoiling inhibition method. The activity of DNA gyrase and topoisomerase IV enzymes showed inhibitory activity (IC50 ) of 6.20 µM and 9.40 µM with compound 7 and 10.14 µM and 13.28 µM with compound 14b, respectively. Surprisingly, exposing compound 7 to gamma irradiation sterilized and increased its activity. Finally, the in-silico analysis predicted that the most active derivatives had good drug-likeness and safe properties. Besides, molecular docking and quantum chemical studies revealed several important interactions inside the active sites and showed the structural features necessary for activity.

Hybridized Quinoline Derivatives as Anticancer Agents: Design, Synthesis, Biological Evaluation and Molecular Docking.

OBJECTIVE: Conjugating quinolones with different bioactive pharmacophores to obtain potent anticancer active agents. METHODS: Fused pyrazolopyrimidoquinolines 3a-d, Schiff bases 5, 6a-e, two hybridized systems: pyrazolochromenquinoline 7 and pyrazolothiazolidinquinoline 8, different substituted thiazoloquinolines 13-15 and thiazolo[3,2-a]pyridine derivatives 16a-c were synthesized. Their chemical structures were characterized through spectral and elemental analysis, cytotoxic activity on five cancer cell lines, caspase-3 activation, tubulin polymerization inhibition and cell cycle analysis were evaluated. RESULTS: Four compounds 3b, 3d, 8 and 13 showed potent activity than doxorubicin on HCT116 and three compounds 3b, 3d and 8 on HEPG2. These promising derivatives showed increase in the level of caspase-3. The trifloromethylphenyl derivatives of pyrazolopyrimidoquinolines 3b and 3d showed considerable tubulin polymerization inhibitory activity. Both compounds arrested cell cycle at G2/M phase and induced apoptosis. CONCLUSION: Compounds 3b and 3d can be considered as promising anticancer active agents with 70% of colchicine activity on tubulin polymerization inhibition and represent hopeful leads that deserve further investigation and optimization.