Novel isoniazid-hydrazone derivatives induce cell growth inhibition, cell cycle arrest and apoptosis via mitochondria-dependent caspase activation and PI3K/AKT inhibition.

In this study, seven isoniazid-hydrazone derivatives (3a-g) were synthesized and their structures elucidated by chromatographic techniques, and then the antiproliferative effects of these compounds on various cancer cells were tested. The advanced anticancer mechanism of the most potent compound was then investigated. Antiproliferative activities of the synthesized compounds were evaluated on human breast cancer MCF-7, lung cancer A-549, colon cancer HT-29, and non-cancerous mouse fibroblast 3T3-L1 cell lines by XTT assay. Flow cytometry analysis were carried out to determine cell cycle distribution, apoptosis, mitochondrial membrane potential, multi-caspase activity, and expression of PI3K/AKT signaling pathway. The XTT results showed that all the title molecules displayed cytotoxic activity at varying strengths in different dose ranges, and among them, the strongest cytotoxic effect and high selectivity were exerted by 3d against MCF-7 cells with the IC50 value of 11.35 µM and selectivity index of 8.65. Flow cytometry results revealed that compound 3d induced apoptosis through mitochondrial membrane disruption and multi-caspase activation in MCF-7 cells. It also inhibited the cell proliferation via inhibition of expression of PI3K/AKT and arrested the cell cycle at G0/G1 phase. In conclusion, all these data disclosed that among the synthesized compounds, 3d is notable for in vivo anticancer studies.

Comparative study of three fingerprint analytical approaches based on spectroscopic sensors and chemometrics for the detection and quantification of argan oil adulteration.

BACKGROUND: Argan oil is one of the purest and rarest oils in the world, so that the addition of any further product is strictly prohibited by international regulations. Consequently, it is necessary to establish reliable analytical methods to ensure its authenticity. In this study, three multivariate approaches have been developed and validated using fluorescence, UV-visible, and attenuated total reflectance Fourier transform mid-infrared (FT-MIR) spectroscopies. RESULTS: The application of a partial least squares discriminant analysis model showed an accuracy of 100%. The quantification of adulteration have been evaluated using partial least squares (PLS) regression. The PLS model developed from fluorescence spectroscopy provided the best results for the calibration and cross-validation sets, as it showed the highest R2 (0.99) and the lowest root mean square error of calibration and cross-validation (0.55, 0.79). The external validation of the three multivariate approaches by the accuracy profile shows that these approaches guarantee reliable and valid results of 0.5-32%, 7-32%, and 10-32% using fluorescence, FT-MIR and UV-visible spectroscopies respectively. CONCLUSION: This study confirmed the feasibility of using spectroscopic sensors (routine technique) for rapid determination of argan oil falsification. © 2021 Society of Chemical Industry.

Chemometric Analysis of UV-Visible Spectral Fingerprints for the Discrimination and Quantification of Clinical Anthracycline Drug Preparation Used in Oncology.

In clinical treatment, the analytical quality assessment of the delivery of chemotherapeutic preparations is required to guarantee the patient's safety regarding the dose and most importantly the appropriate anticancer drug. On its own, the development of rapid analytical methods allowing both qualitative and quantitative control of the formulation of prepared solutions could significantly enhance the hospital's workflow, reducing costs, and potentially providing optimal patient care. UV-visible spectroscopy is a nondestructive, fast, and economical technique for molecular characterization of samples. A discrimination and quantification study of three chemotherapeutic drugs doxorubicin, daunorubicin, and epirubicin was conducted, using clinically relevant concentration ranges prepared in 0.9% NaCl solutions. The application of the partial least square discriminant analysis PLS-DA method on the UV-visible spectral data shows a perfect discrimination of the three drugs with a sensitivity and specificity of 100%. The use of partial least square regression PLS shows high quantification performance of these molecules in solution represented by the low value of root mean square error of calibration (RMSEC) and root mean square error of cross validation (RMSCECV) on the one hand and the high value of R-square on the other hand. This study demonstrated the viability of UV-visible fingerprinting (routine approach) coupled with chemometric tools for the classification and quantification of chemotherapeutic drugs during clinical preparation.

E-Cigarette Quality Control: Impurity and Nicotine Level Analysis in Electronic Cigarette Refill Liquids.

This work targets mainly the quality control of electronic cigarette liquids. It relies on an analytical control of a "32-product" sample made of several types of e-cigarette liquids taken from various supermarkets and tobacconist's offices in Morocco. All along this study, we made sure to check both the conformity of the nicotine level indicated in the packaging of each product and the existence of any other components inside the product, especially toxic or unknown impurities. The method used for this study is known under the name of high-performance liquid chromatography. For statistical analysis, we used Student's t-test for a single sample in order to analyze the relative differences between nicotine quantity reported in the product and the one measured during our experiment. Finally, we used linear regression test to determine the relationship between the nicotine level accuracy on the packaging and the level of toxic impurities in the products. The differences between the nicotine concentrations reported in the packages and the measured ones varied from -100% to +3.3%. The study showed that 31% of analyzed products have an accurate indication of the level of nicotine on the packaging. However, 47% of the studied products showed more than 20% difference between measure and packaging indication. In all analyzed samples, the level of impurities altered from 0 to 32.6%. Furthermore, the level of the nicotine breakdown products did not exceed 2% of the nicotine content in pretty much all of the samples. The actual nicotine content of electronic cigarette refill liquids is not always as precise as what is stated on the packaging; in addition to the level of impurities detected in several brands and that exceeds the European Pharmacopoeia standards, some may even present a risk of causing toxicological damage.

Phytochemical Characterization, Antioxidant and In Vitro Cytotoxic Activity Evaluation of Juniperus oxycedrus Subsp. oxycedrus Needles and Berries.

In order to evaluate the antioxidant properties of aqueous and methanol extracts of needles and berries of Juniperus oxycedrus subsp. oxycedrus (Joo) species, various antioxidant capacity assessment tests (free radical scavenging assays (DPPH• and ABTS•+ tests), ferrous ions (Fe2+) chelating activity and reducing power assay (FRAP) were conducted. In all of the tests, the extracts exhibited strong antioxidant activity. Furthermore, in-vitro cytotoxic activity assays of the methanolic extracts showed potent cytotoxic effects against two breast cancer cell lines (MDA-MB-468 and MCF-7), with no cytotoxicity towards normal cells (PBMCs). Reactive oxygen species generation was presumed to be a potential reason for the observed cytotoxic effects. According to all the above, and considering its appropriate composition of mineral elements and phenolic compounds, Joo could offer a beneficial and natural source of bioactive compounds that can be either used on the preventive side as it could potentially be used in the clinic without toxicity.

Oil shale powders and their interactions with ciprofloxacin, ofloxacin, and oxytetracycline antibiotics.

The interaction of oil shale, as a widespread sedimentary rock, with common antibiotics ofloxacine, oxytetracycline, and ciprofloxacine was studied. The selected Moroccan deposit and its thermally treated forms were fully characterized from a chemical and structural point of view, indicating the prevalence of quartz as a mineral component together with aluminum- and iron-rich phase that are converted into Al-doped iron oxide phases upon heating. The presence of 4 wt% organics was also detected, which was removed at 550 °C without significant loss of specific surface area. The pseudo-second-order kinetic model and Langmuir equation were found the most adequate to reproduce the kinetics and isothermal sorption experiments. These analyses enlighten the contribution of the organic matter on antibiotic retention as well as the key role of hydrophobic interactions on the molecule-mineral surface interactions. Our results emphasize the possible contribution of raw oil shale in the accumulation of antibiotics in soils and suggest that thermally treated oil shell powders can constitute cheap mineral sorbents for environmental cleaning.