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A new series of thirty-one quinazolinone–chalcone hybrid molecules 13–43 were designed, synthesized, and structurally characterized by different spectroscopic techniques. All the synthesized compounds were investigated for in vitro cytotoxic activity against five human cancer cell lines namely, epidermoid carcinoma A431, lung adenocarcinoma A549, fibrosarcoma HT-1080, mammary adenocarcinoma MDA-MB-231, and prostate adenocarcinoma PC-3, as well as normal AG01523 cells using the MTT assay. Most of the new hybrids showed remarkable cytotoxic activity in the low micromolar range. Compounds 20, 22, 28, 33, 39, 40, and 41 had shown the highest cytotoxicity among the tested compounds against the epidermoid carcinoma A431 with IC50 ranging from 1 to 2 μM. Notably, the tested compounds displayed no or little cytotoxicity against the normal human skin fibroblasts. Moreover, flow cytometric cell cycle analysis performed on A431 cells revealed that the most cytotoxic compounds arrested A431 cells in the S- or G2/M-phase or both and induced a marked increase in the percentage of subdiploid events, indicating the stimulation of cell death by apoptosis. A further mechanistic study demonstrated that quinazolinone–chalcone hybrids induced apoptosis via induction of caspase-3 and PARP-1 cleavage. Moreover, a molecular docking study was performed for the target chalcones to investigate their mode of binding to PARP-1. Finally, a conclusive structure–activity relationship (SAR) study was formulated to facilitate the future design of powerful apoptotic candidates targeting both caspase-3 and PARP-1 proteins. [ABSTRACT FROM AUTHOR]

This article presents a continuous capillary electrophoresis with laser‐induced fluorescence (CE‐LIF) following spectral studies of the noncovalent interactions between novel Squarylium Boronic Acid 4 (SQ‐BA4) & Squarylium Diboronic Acid 2 (SQ‐DBA2) squarylium dyes and human serum albumin (HSA). Two protocols were used wherein the on‐column‐labeling protocol was found to be more sensitive than the precolumn one by showing a better enhancement in the peak area of the HSA–dye complex besides lower limits of detection (LODs) for HSA. Also, stability studies were conducted with or without HSA using precolumn‐labeling mode over one week exhibiting the superiority of SQ‐BA4 to SQ‐DBA2. Then, a mixture containing three model proteins, HSA, β‐lactoglobulin B, and transferrin, was labeled on‐column with both dyes and completely resolved by CE‐LIF after optimization of several parameters. Both dyes provided lower LODs for HSA than those of β‐lactoglobulin B and transferrin with higher sensitivities. In addition, the SQ‐BA4 dye showed again greater sensitivities with all the three proteins than SQ‐DBA2. Novel SQ‐BA4 & SQ‐DBA2 squarylium dyes can be used as fluorescent probes for human serum albumin, β‐lactoglobulin B, and transferrin through noncovalent interaction using capillary electrophoresis with laser‐induced fluorescence. [ABSTRACT FROM AUTHOR]

A suitable HPLC method has been selected and validated for rapid simultaneous separation and determination of four imidazole anti-infective drugs, secnidazole, omeprazole, albendazole, and fenbendazole, in their final dosage forms, in addition to human plasma within 5 min. The method suitability was derived from the superiority of using the environmentally benign solvent, methanol over acetonitrile as a mobile phase component in respect of safety issues and migration times. Separation of the four anti-infective drugs was performed on a Thermo Scientific® BDS Hypersil C8 column (5 µm, 2.50 × 4.60 mm) using a mobile phase consist of MeOH: 0.025 M KH2PO4 (70:30, v/v) adjusted to pH 3.20 with ortho-phosphoric acid at room temperature. The flow rate was 1.00 mL/min and maximum absorption was measured with UV detector set at 300 nm. Limits of detection were reported to be 0.41, 0.13, 0.18, and 0.15 µg/mL for secnidazole, omeprazole, albendazole, and fenbendazole, respectively, showing a high degree of the method sensitivity. The method of analysis was validated according to Food and Drug Administration (FDA)guidelines for the determination of the drugs, either in their dosage forms with highly precise recoveries, or clinically in human plasma, especially regarding pharmacokinetic and bioequivalence studies. [ABSTRACT FROM AUTHOR]

Background: Allergic diseases are considered as the major burden on public health with increased prevalence globally. Histamine H1-receptor antagonists are the foremost commonly used drugs in the treatment of allergic disorders. The target drug in this study, loratadine, belongs to this class of drugs and its biometabolite desloratadine which is also a non-sedating H1 receptor antagonist with anti-histaminic activity being 2.5 to 4 times greater than loratadine. This study aimed to develop and validate a novel isocratic Reversed-phase High-Performance Liquid Chromatography (RP-HPLC) method for rapid and simultaneous separation and determination of loratadine and its metabolite, desloratadine in human plasma., Methods: The drug extraction method from plasma was based on protein precipitation technique. The separation was carried out on a Thermo Scientific BDS Hypersil C18 column (5μm, 250 x 4.60 mm) in a mobile phase of MeOH: 0.025M KH2PO4 adjusted to pH 3.50 using orthophosphoric acid (85: 15, v/v) at an ambient temperature. The flow rate was maintained at 1 mL/min and maximum absorption was measured using the PDA detector at 248 nm., Results: The retention times of loratadine and desloratadine in plasma samples were recorded to be 4.10 and 5.08 minutes, respectively, indicating a short analysis time. Limits of detection were found to be 1.80 and 1.97 ng/mL for loratadine and desloratadine, respectively, showing a high degree of sensitivity of the method. The method was then validated according to FDA guidelines for the determination of the two analytes in human plasma., Conclusion: The results obtained indicate that the proposed method is rapid, sensitive in the nanogram range, accurate, selective, robust and reproducible compared to other reported methods., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)