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Background: Duvelisib (DUV) is a new oral phosphoinositide-3-kinase (PI3K)-δ and PI3K-γ inhibitor. It has been recently granted an accelerated approval for treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). It is also effective in therapy of T-cell lymphoma, solid tumors, and non-Hodgkin's lymphoma. In literature, there is no method valid for quantitation of DUV in human plasma for its therapeutic monitoring and pharmacokinetic studies., Purpose: The purpose of this study is the establishment of a highly sensitive HPLC method with fluorescence detection for quantitation of DUV in plasma for its therapeutic monitoring and pharmacokinetic studies of DUV., Methods: The resolution of DUV and the internal standard (IS) olaparib (OLA) was achieved on Nucleosil CN column, with a mobile phase composed of acetonitrile:water (25:75, v/v) at a flow rate of 1.7 mL min -1 . The fluorescence of both DUV and OLA was detected at 410 nm after excitation at 280 nm. The method was validated according to the guidelines of bioanalytical method validation., Results: The method was linear in the range of 5-100 ng mL -1 , and its limit of detection (LOD) and limit of quantitation (LOQ) were 2.12 ng mL -1 and 7 ng mL -1 , respectively. The precisions of the method were ≤ 8.26%, and its accuracies were ≥ 95.32%. All the other validation parameters were satisfactory. The proposed method was successfully employed to the investigation of the pharmacokinetic profile of DUV in rats following a 25 mg/kg single dose of oral administration., Conclusion: The method is characterized with high sensitivity, accuracy, simple sample pretreatment, rapidity, eco-friendly as it consumes low volumes of organic solvent in the mobile phase and has high analysis throughput as its run time was short (~ 10 min)., Competing Interests: The authors report no conflicts of interest for this work., (© 2021 Sayed et al.)

Purpose: The objective of our work was to prepare a potent and safe antimicrobial and anticancer agents, through synthesis of several peptides and examine their biological activities, namely as, cytotoxically potent and antimicrobial and antifungal agents., Introduction: Multidrug-resistant microbial strains have arisen against all antibiotics in clinical use. Infections caused by these bacteria threaten global public health and are associated with high mortality rates., Methods: The main backbone structure for the novel synthesized linear peptide is Nα-1, 3-benzenedicarbonyl-bis-(Amino acids)-X, ( 3-11 ). A computational docking study against DNA gyrase was performed to formulate a mode of action of the small compounds as antimicrobial agents., Results: The peptide-bearing methionine-ester ( 4 ) exhibited potent antimicrobial activity compared to the other synthesized compounds, while, peptide ( 8 ), which had methionine-hydrazide fragment was the most potent as antifungal agent against Aspergillus niger with 100% inhibition percent. Compounds ( 6 and 7 ) showed the highest potency against breast human tumor cell line "MCF-7" with 95.1% and 79.8% of cell inhibition, respectively. The nine compounds possessed weak to moderate antiproliferative effect over colon tumor cell line. The docking results suggest good fitting through different hydrogen bond interactions with the protein residues. In silico ADMET study also evaluated and suggested that these compounds had promising oral bioavailability features., Conclusion: The tested compounds need further modification to have significant antimicrobial and antitumor efficacy compared to the reference drugs., Competing Interests: The authors declare no conflicts of interest in this work., (© 2021 Naglah et al.)