Mini Reviews in Medicinal Chemistry - Volume 19, Issue 11, 2019

Background: Cannabis use has increased over the past several years as some countries have legalized its use for the treatment of certain medical conditions and/or for recreational use. Thus, concerns have risen about potential adverse health effects. Increasing number of reports have associated cannabis use with serious cardiovascular (CV) complications. Furthermore, there appears to be a likeness in the harmful health effects, especially on the CV and respiratory systems, of cannabis smoking to those of tobacco smoking. Objective: To review the CV effects of cannabis use and compare them with those of tobacco use. Methods: Articles were reviewed that were published in English literature reporting on cannabis and cannabinoid pharmacology and their effects on the CV system and their consequences. Emphasis was also placed on articles reporting on cannabis use in adolescents, exposure to secondhand smoke, its effect on exercise and finally its inter-relationship and similarities with tobacco use. Results: With growing cannabis use, an increasing number of reports have emerged associating marijuana use with serious and life-threatening CV complications, including acute coronary syndromes, potentially lethal cardiac arrhythmias and ischemic strokes. There are certain similarities of the deleterious CV and respiratory effects of cannabis smoking with those of tobacco smoking. Despite the difference in the active ingredients (tetrahydrocannabinol vs. nicotine), each substance produces a plethora of chemicals when smoked and these are largely identical; furthermore, due to different modes of smoking, cannabis chemicals are retained in the body for a longer time. Of course, concomitant tobacco and cannabis smoking is a perplexing factor in isolating damages specifically pertaining to cannabis use, while the health risk is additive. Although the mechanisms producing CV harm may be somewhat different between these two substances, the outcome appears similar, or even worse, as the effects may emerge at a younger age. Conclusion: There is an increasing concern that, apart from the mental health problem with cannabis smoking, societies may be facing another wave of a déjà vu/déjà vécu phenomenon similar to the tobacco smoking story.

Type-2 Diabetes (T2D) is a metabolic disease characterized by permanent hyperglycemia, whose development can be prevented or delayed by using therapeutic agents and implementing lifestyle changes. Some therapeutic alternatives include regulation of glycemia through modulation of different mediators and enzymes, such as AMP-activated protein kinase (AMPK), a highly relevant cellular energy sensor for metabolic homeostasis regulation, with particular relevance in the modulation of liver and muscle insulin sensitivity. This makes it a potential therapeutic target for antidiabetic drugs. In fact, some of them are standard drugs used for treatment of T2D, such as biguanides and thiazolidindiones. In this review, we compile the principal natural products that are activators of AMPK and their effect on glucose metabolism, which could make them candidates as future antidiabetic agents. Phenolics such as flavonoids and resveratrol, alkaloids such as berberine, and some saponins are potential natural activators of AMPK with a potential future as antidiabetic drugs.

Background: In this study, the essential oil composition and cytotoxic activities of five Artemisia species were determined. Methods: The collected plants were water-distilled separately to obtain oils which were then subjected to gas chromatography (GC) and gas chromatography/mass spectrometry GC/MS analyses to identify their compositions. Cancer cells were exposed to different concentrations of samples and cell viability was measured using AlamarBlue® assay. Apoptotic cells were analyzed by propidium iodide (PI) staining and flow cytometry. Results & Conclusion: To study the amount of pro-apoptotic proteins and the apoptosis mechanism, Western blot method was used. Although all samples were cytotoxic at the highest concentration, the oil of A. kulbadica showed the strongest activity among other plants. Carvacrol (IC50 21.11 μg/ml) had the most cytotoxic effects among other components. Carvacrol, 1,8-cineole and 4-terpineole caused an increase in the amount of Bax protein and cleaved peroxisome proliferator-activated receptors (PPAR) and caspase proteins in DU 145 cells.

Background: Due to the side effects of clinically approved anticancer drugs there is a great need to explore and develop new metal-based anticancer drug molecules of high efficiency with less or no side effects. Objective: To synthesize new metal complexes of 2-hydrazinobenzothiazole (hbt) and to investigate their potential anticancer characteristics. Methods: New five complexes; [VO(hbt)2SO4].4H2O (1), [Ru(hbt)2Cl3(H2O)] (2), [M(hbt)2Cl2] [M(II) = Pd (3), Pt (4)] and [Ag(hbt)2].NO3 (5) were prepared and their structure was investigated by means of FTIR, 1H NMR, ESI-MS and UV-Vis spectra, elemental and thermal analysis, magnetic and molar conductance measurements. The ligand and its complexes were examined as anticancer agents against Ehrlich ascites carcinoma (EAC) and human cancer cells (hepatocellular carcinoma Hep-G2, mammary gland breast cancer MCF-7 and colorectal carcinoma HCT-116). This feature is further supported by the DNAmetal complexes binding ability. In addition, anti-oxidation activity of the complexes was investigated. Results: Complex (5) shows the highest anticancer activity with IC50 of 5.15, 9.9, 13.1 and 17.7 μg/mL for EAC, HePG-2, MCF-7 and HCT-116, respectively. Complexes (2) and (3) show promising cytotoxicity against EAC and HePG-2 cells with IC50 5.49 and 16.2 μg/mL, respectively. While, complexes (1) and (4) show optimistic cytotoxicity against EAC with IC50 of 9.63 and 11.25 μg/mL, respectively. The order of DNA binding ability of the complexes is (5) > (3) > (2) > (1) > (4). Among the five complexes, complex (5) shows the best anti-oxidation activity. Conclusion: Complex (5) showed the highest DNA binding ability, anti-oxidation and anticancer activities.

Objectives: Staphylococcus aureus, a Gram-positive bacteria, is ranked second among the causes of hospital infections and is one of the three main causes of food poisoning. In recent times, the spread of antibiotic resistance in S. aureus has become very worrisome. Therefore, research for new effective drugs is important. The present study aims to investigate the phytochemical profiles and antibacterial effects of hydroalcoholic extracts of Origanum vulgare (Lamiaceae family) and Hypericum perforatum (Clusiaceae family) and their active compounds on S. aureus (ATCC 12600) in vitro. Methods: The identification of phytochemical compounds in both plants was performed by Highperformance liquid chromatography (HPLC), headspace-solid-phase microextraction (HS-SPME) and Fourier-transform infrared spectroscopy (FTIR). To investigate microbial susceptibility, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and disc diffusion method (DAD) were used. Finally, the results of the study were compared with methicillin. Results: Of the 42 combinations of O. vulgare, carvacrol (48%) and of the 38 combinations of H. perforatum, hypericin (46.2%) were the most abundant. The MIC, MBC and DAD of O. vulgare and H. perforatum, carvacrol, hypericin and methicillin were 625, 625, 312.5, 78.12 and 384 μg/mL, 10000, 10000, 2500, 2500 and 384 μg/mL, and 15.66 ± 4.49, 12.66 ± 0.47 and 22 ± 0.81 mm, respectively. Conclusion: Due to the significant effects of O. vulgare and H. perforatum and their active components against S. aureus, it is expected that in the future, hypericin, carvacrol and their derivatives can be used as effective antibacterial agents against S. aureus.

Background & Objective: The target tetrazole glycosides were synthesized by construction of ring system by cycloaddition reaction of benzothiazole-linked nitrile derivative and sodium azide followed by N-glycosylation process and deprotection. Methods: The triazole glycosides were prepared by applying click approach involving dipolar cycloaddition of benzothiazole possessing alkyne functionality and different glycosyl azides. The products incorporating acyclic analogs of sugar moieties were synthesized through alkylation using acyclic oxygenated halides. Results: The anticancer activity was studied against human breast adenocarcinoma cells (MCF-7) and human normal Retina pigmented epithelium cells (RPE-1). High activities were revealed by three compounds with IC50 values 11.9-16.5 μM compared to doxorubicin (18.6 μM) in addition to other four derivatives with good inhibition activities. Conclusion: Enzyme docking investigation was performed into cyclin-dependent kinase 2 (CDK2); a potential target for cancer medication. Compounds which have possessed highest activities revealed good fitting inside the binding site of the protein molecular surface and showed minimum binding energy.