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Ahmed M Naglah,1,2 Gaber O Moustafa,2 Ahmed A Elhenawy,3,4 Marwa M Mounier,5 Heba El-Sayed,6 Mohamed A Al-Omar,1 Abdulrahman A Almehizia,1,7 Mashooq A Bhat7 1Department of Pharmaceutical Chemistry, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia; 2Peptide Chemistry Department, Chemical Industries Research Division, National Research Centre, Cairo, Egypt; 3Chemistry Department, Faculty of Science, Al-Azhar University (Boys’Branch), Cairo, Egypt; 4Chemistry Department, Faculty of Science, Albaha University, Al Baha, Saudi Arabia; 5Pharmacognosy Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Giza, Egypt; 6Botany and Microbiology Department, Faculty of Science, Helwan University, Helwan, Egypt; 7Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi ArabiaCorrespondence: Gaber O Moustafa; Ahmed Elhenawy Tel +201003123355; +966599044526Email gosman79@gmail.com; elhenawy_sci@hotmail.comPurpose: 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)

Ahmed Y Sayed, Nasr Y Khalil, Aliyah Almomen, Nourah Z Alzoman, Abdulrahman A Almehizia, Ibrahim A Darwish Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi ArabiaCorrespondence: Ibrahim A DarwishDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi ArabiaTel +966-114677348Fax +966-114676220Email idarwish@ksu.edu.saBackground: 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

Cannabinoid receptors 1 and 2 (CB1 and CB2) belong to the rhodopsin-like family of the G-Protein Coupled Receptors (GPCRs). CB1 receptors are highly expressed in the central nervous system, while CB2 receptors are expressed mainly in the immune cells and the periphery. Targeting the CB2 receptors is believed to avoid the psychoactive side effects associated with CB1 receptors. CB2 receptors have been shown to be involved in several physiological functions as well as diseases, such as pain, multiple sclerosis, osteoporosis, and cancer demonstrating the importance of the CB2 receptors. In the present study, we employed chemistry design and discovery to identify novel CB2 ligands, carried out in-vitro functional studies, and evaluated the therapeutic potentials. Several chemical scaffolds were discovered and evaluated. The di-amide scaffold was discovered utilizing pharmacophore drug discovery and molecular docking studies. Several derivatives of the di-amide scaffold demonstrated potent and highly selective CB2 inverse agonists as well as potent anti-osteoclast formation capabilities. The di-amide derivatives suffered from weak anti-multiple myeloma (MM) properties and poor pharmacokinetic properties. A new scaffold was identified utilizing scaffold hopping and molecular docking studies. However, the 2-(sulfonylamino)-2-phenylacetamide scaffold demonstrated weak CB2 binding affinity. Due to the limitation of the two previous scaffolds, virtual high-throughput screening as well as structure-based drug design were utilized for scaffold hopping in order to identify new CB2 scaffolds. A new lead compound was identified and structure activity relationship (SAR) studies were conducted on the scaffold 4-(aminomethyl)-N,N-diethylaniline. Several novel compounds were discovered with high potency and selectivity. Functional experiments showed different functionality (agonist and inverse agonist) of these compounds. Nevertheless, therapeutic studies showed that inverse agonism i

Cannabinoid receptors 1 and 2 (CB1 and CB2) belong to the rhodopsin-like family of the G-Protein Coupled Receptors (GPCRs). CB1 receptors are highly expressed in the central nervous system, while CB2 receptors are expressed mainly in the immune cells and the periphery. Targeting the CB2 receptors is believed to avoid the psychoactive side effects associated with CB1 receptors. CB2 receptors have been shown to be involved in several physiological functions as well as diseases, such as pain, multiple sclerosis, osteoporosis, and cancer demonstrating the importance of the CB2 receptors. In the present study, we employed chemistry design and discovery to identify novel CB2 ligands, carried out in-vitro functional studies, and evaluated the therapeutic potentials. Several chemical scaffolds were discovered and evaluated. The di-amide scaffold was discovered utilizing pharmacophore drug discovery and molecular docking studies. Several derivatives of the di-amide scaffold demonstrated potent and highly selective CB2 inverse agonists as well as potent anti-osteoclast formation capabilities. The di-amide derivatives suffered from weak anti-multiple myeloma (MM) properties and poor pharmacokinetic properties. A new scaffold was identified utilizing scaffold hopping and molecular docking studies. However, the 2-(sulfonylamino)-2-phenylacetamide scaffold demonstrated weak CB2 binding affinity. Due to the limitation of the two previous scaffolds, virtual high-throughput screening as well as structure-based drug design were utilized for scaffold hopping in order to identify new CB2 scaffolds. A new lead compound was identified and structure activity relationship (SAR) studies were conducted on the scaffold 4-(aminomethyl)-N,N-diethylaniline. Several novel compounds were discovered with high potency and selectivity. Functional experiments showed different functionality (agonist and inverse agonist) of these compounds. Nevertheless, therapeutic studies showed that inverse agonism i