Comtrifosides A and B, two new triterpenoid saponins from the leaves of Combretum trifoliatum.

The phytochemical composition of the Combretum trifoliatum leaves was studied for the first time. Two new triterpenoid saponins, named comtrifoside A (1) and comtrifoside B (2), together with two other saponins (3-4) were purified by variously chromatographic techniques. For the first time, compound 3 was informed from the Combretum genus, as well as all of the isolated compounds (1-4) were reported from C. trifoliatum. The chemical structures of them were clearly characterised using extensive UV-VIS, IR, HRMS-ESI, and NMR experimental data. The in vitro anti-inflammatory activities of 1 & 2 were examined against NO overproduction in LPS activation of RAW264.7.

Exploration of Remarkably Potential Multitarget-Directed N-Alkylated-2-(substituted phenyl)-1H-benzimidazole Derivatives as Antiproliferative, Antifungal, and Antibacterial Agents.

Improving lipophilicity for drugs to penetrate the lipid membrane and decreasing bacterial and fungal coinfections for patients with cancer pose challenges in the drug development process. Here, a series of new N-alkylated-2-(substituted phenyl)-1H-benzimidazole derivatives were synthesized and characterized by 1H and 13C NMR, FTIR, and HRMS spectrum analyses to address these difficulties. All the compounds were evaluated for their antiproliferative, antibacterial, and antifungal activities. Results indicated that compound 2g exhibited the best antiproliferative activity against the MDA-MB-231 cell line and also displayed significant inhibition at minimal inhibitory concentration (MIC) values of 8, 4, and 4 µg mL-1 against Streptococcus faecalis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus compared with amikacin. The antifungal data of compounds 1b, 1c, 2e, and 2g revealed their moderate activities toward Candida albicans and Aspergillus niger, with MIC values of 64 µg mL-1 for both strains. Finally, the molecular docking study found that 2g interacted with crucial amino acids in the binding site of complex dihydrofolate reductase with nicotinamide adenine dinucleotide phosphate.

Metal complexes of benzimidazole-derived as potential anti-cancer agents: synthesis, characterization, combined experimental and computational studies.

In this study, a series of 14 Cu (II), Zn (II), Ni (II) and Ag (I) complexes containing bis-benzimidazole derivatives were successfully designed and synthesized from 2-(1H-benzimidazole-2-yl)-phenol derivatives and corresponding metal salt solutions. The compound structures were identified by FT-IR, 1H-NMR, powder X-ray diffraction and ESI-MS analyses, and the presence of the metal in the complexes was confirmed by ultraviolet-visible spectroscopy and ICP optical emission spectrometry. Electronic structure calculations were also carried out to describe the detailed structures in addition to the electronic absorption spectra of the ligands. The cytotoxic activity of the complexes was evaluated against three human cancer cell lines: lung (A549), breast (MDA-MB-231) and prostate (PC3) cancer cells. All complexes inhibited anti-proliferative cancer cells better than free ligands, especially Zn (II) and Ag (I) complexes, which are most sensitive to MDA-MB-231 cells. In addition, showing the growth inhibition of three cancer cell lines with IC50 < 10.4 µM, complexes C1 , C3 and C14 could be considered potential multi-targeted anti-cancer agents.

Synthesis and insight into the structure-activity relationships of 2-phenylbenzimidazoles as prospective anticancer agents.

In order to explore and develop new anticancer agents, three series of 2-phenylbenzimidazoles, 15-46, were condensed under simple and mild conditions using sodium metabisulfite as an oxidation agent and another series, 47-55, were obtained via a reduction reaction using sodium borohydride. All the compounds synthesized were evaluated for their in vitro anticancer activities against three human cancer cell lines. The novel compound 38 was found to be the most potent multi cancer inhibitor against A549, MDA-MB-231, and PC3 cell lines (IC50 values 4.47, 4.68 and 5.50 µg mL-1, respectively). In addition, compound 40 exhibited the best IC50 value of 3.55 µg mL-1 against the MDA-MB-231 cell line. The results demonstrated that introducing a new substituent to compounds 37-55 could improve their antiproliferative activities.

Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women not exposed to oxytocin during labour: a double-blind, randomised, non-inferiority trial.

BACKGROUND: Oxytocin, the standard of care for treatment of post-partum haemorrhage, is not available in all settings because of refrigeration requirements and the need for intravenous administration. Misoprostol, an effective uterotonic agent with several advantages for resource-poor settings, has been investigated as an alternative. This trial established whether sublingual misoprostol was similarly efficacious to intravenous oxytocin for treatment of post-partum haemorrhage in women not exposed to oxytocin during labour. METHODS: In this double-blind, non-inferiority trial, 9348 women not exposed to prophylactic oxytocin had blood loss measured after vaginal delivery at four hospitals in Ecuador, Egypt, and Vietnam (one secondary-level and three tertiary-level facilities). 978 (10%) women were diagnosed with primary post-partum haemorrhage and were randomly assigned to receive 800 microg misoprostol (n=488) or 40 IU intravenous oxytocin (n=490). Providers and women were masked to treatment assignment. Primary endpoints were cessation of active bleeding within 20 min and additional blood loss of 300 mL or more after treatment. Clinical equivalence of misoprostol would be accepted if the upper bound of the 97.5% CI fell below the predefined non-inferiority margin of 6%. All outcomes were assessed from the time of initial treatment. This study is registered with ClinicalTrials.gov, number NCT00116350. FINDINGS: All randomly assigned participants were analysed. Active bleeding was controlled within 20 min with study treatment alone for 440 (90%) women given misoprostol and 468 (96%) given oxytocin (relative risk [RR] 0.94, 95% CI 0.91-0.98; crude difference 5.3%, 95% CI 2.6-8.6). Additional blood loss of 300 mL or greater after treatment occurred for 147 (30%) of women receiving misoprostol and 83 (17%) receiving oxytocin (RR 1.78, 95% CI 1.40-2.26). Shivering (229 [47%] vs 82 [17%]; RR 2.80, 95% CI 2.25-3.49) and fever (217 [44%] vs 27 [6%]; 8.07, 5.52-11.8) were significantly more common with misoprostol than with oxytocin. No women had hysterectomies or died. INTERPRETATION: In settings in which use of oxytocin is not feasible, misoprostol might be a suitable first-line treatment alternative for post-partum haemorrhage.