Springer Science and Business Media LLC

A simple, precise, rapid, selective, and economic high performance thin-layer chromatography method has been established for simultaneous analysis of atorvastatin (ATV) and ezetimibe (EZE) in tablet dosage forms. The chromatography separation was performed on precoated silica gel 60 GF254 plates with toluene–ethyl acetate–methanol 12:5:3 (v/v/v) as mobile phase. The plate was developed to a distance of 8.0 cm at ambient temperature. The retention factors for ATV and EZE were 0.31 and 0.57, respectively. The detection band was carried out at 254 nm. The calibration curve was linear in the concentration range of 200–1200 ng/spot for both ATV and EZE. For ATV, the recovery study results ranged from 99.44 to 99.54% with RSD value ranging from 0.067 to 0.107%. For EZE, the recovery results ranged from 98.88 to 99.00% with RSD value ranging from 0.154 to 1.756%. The assay was 99.89% for ATV and 99.84% for EZE. The calibration plots revealed a good linear relationship with r 2 = 0.9991 for ATV and 0.9992 for EZE. Both ATV and EZE were subjected to different stress conditions—acid, alkaline hydrolysis, oxidation, photo degradation, dry, and wet heat treatment—as prescribed by ICH. The degradation products were well resolved from the pure drug with significantly different R f values. The method was validated for precision, accuracy, specificity, ruggedness, and robustness.

During the last years, the progression to control malaria disease seems to be slowed and WHO (World Health Organization) reported a modeling analysis with the prediction of the increase in malaria morbidity and mortality in sub-Saharan Africa during the COVID-19 pandemic. A rapid way to the discovery of new drugs could be carried out by performing investigations to identify drugs based on repurposing of “old” drugs. The 5-nitrothiazole drug, Nitazoxanide was shown to be active against intestinal protozoa, human helminths, anaerobic bacteria, viruses, etc. In this work, Nitazoxanide and analogs were prepared using two methodologies and evaluated against P. falciparum 3D7. A bithiazole analog, showed attractive inhibitory activity with an EC50 value of 5.9 μM, low propensity to show toxic effect against HepG2 cells at 25 μM, and no cross-resistance with standard antimalarials.

The discovery of three new natural products (1, 4, and 5), one semi-synthetic derivative (3) along with two known compounds (2 and 6) were isolated from an endophytic fungus Cryptosporiopsis sp. The structural elucidations of 1–6 were authenticated by one-dimensional and two-dimensional nuclear magnetic resonance, mass spectroscopy, and X-ray diffraction analysis. Herein, we intervention of diazomethane as tool that help in the crystallization and isolation of inseparable mixtures of compounds 1 and 2. Compounds (1–6) were screened for cytotoxic activity against six cancer cell lines in which the 4-epi-ethisolide (2) exhibited moderate activity with IC50 values 11 µM in HL-60, whereas the compound 3 lost its cytotoxic potentiality, but it displayed moderate antimicrobial activity. The result illustrates that the methylene moiety in 2 plays significant role in cytotoxic potential.

In the present study, 4-amino-1,2-naphthoquinone analogues were synthesized and characterized by spectroscopic (FT-IR, 1H NMR and 13C NMR) and elemental analysis. The synthesized compounds were evaluated for anticonvulsant activity by the maximal electroshock (MES) test and subcutaneous pentylenetetrazole (sc. PTZ) test, the most widely employed seizure models for early identification of anticonvulsant candidates, whereas their neurotoxicity was examined by rotarod test. Compounds were administered to animals at different concentrations (10, 20 & 40 mg/kg) by intraperitonial (i.p.) route and the % seizure protection was measured. The pharmacological results revealed that majority of compounds were effective in MES and sc. PTZ tests. Compounds N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)butyramide (4) and N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)-3-methylbutanamide (6) were active at the dose 40 & 20 mg/kg, respectively, while compounds N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)hexanamide (7) and 4-acetamido-N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)benzamide (10) were active at the dose 10 mg/kg and emerged as the most active compounds of the series. These compounds showed anticonvulsant effect comparable to phenytoin which was used as reference antiepileptic drug. The above-mentioned compounds have diminutive neurotoxic effects so they can move on next phase of anticonvulsant drug development.

Nine N-alkylated derivatives of riluzole were synthesized in order to obtain new compounds with potential antinociceptive activity. Riluzole was firstly transformed into (6-trifluoromethoxy-benzothiazol-2-yl)-hydrazine, then it was chlorinated by SOCl2 to obtain 2-chloro-6-trifluoromethoxy-benzothiazole. This intermediate product was treated with nine alkylamines to give N-alkylated derivatives of riluzole respectively. The structures of compounds were confirmed by means of elemental analysis, IR, 1H NMR, and 13C NMR. The synthetic route was optimized and four novel crystals were obtained by recrystallization. This study investigated the antinociceptive activity of some N-alkylated derivatives of riluzole by hot plate test in mice. The relationship between antinociceptive activity and the doses of 4b, 4c, 4h, 4g, and riluzole had been studied. Compared with the control group (0 mg/kg), the effects of compounds 4b and 4h showed a significant increase (13.78 ± 2.89 s, 12.89 ± 2.94 s, respectively). Compound 4c showed extreme significant increase (18.07 ± 3.08 s) in the time mice spent on the hot plate. The compounds 4b, 4c, and 4h had increased the latency time compared to the blank solvent group. They have potential application in developing new drug candidates with antinociceptive activity.

A series of twelve 4-methyl-2-(2-, 3- and 4-pyridinyl)quinolines 7–9 was synthesized using modified Kametani reaction protocol and their in vitro cytotoxicity was tested against human cancer cell lines MCF-7, SKBR-3, PC3, HeLa, comparing with human dermis fibroblast as non-tumor cells. In general, these molecules displayed potent anticancer properties, but also demonstrated a narrow safe margin, as it was observed for doxorubicin. Compounds 8a, 8b, 9a and 9d showed prominent selective cytotoxicity with higher IC50 values compared with reference drug doxorubicin in prostate carcinoma, cervical epithelial carcinoma and breast carcinoma (no overexpresses the HER2/c-erb-2 gene), respectively. The 4-methyl-2-(3-pyridinyl)quinoline (8a) stands out by its low unspecific cytotoxicity (IC50 = 476.69 μM) and highly exceptional selectivity for PC3 cells (IC50 = 4.40 μM) as an interesting model for antitumor drugs against prostate carcinoma. Its 4-pyridinyl analog 9a showed superior potency against HeLa cells (IC50 = 0.016 μM) and an outstanding selectivity (SI = 4168.1) compared to doxorubicin (IC50 = 3.62 µM, SI = 0.7). Analog 9d revealed potent activity (IC50 = 0.38 µM) against breast cancer MCF-7. In silico studies are also reported. ADME profiling, in silico toxicity and drug-score data of compounds 8a and 9a resulted to be favorable compared to doxorubicin.