title: Synthesis, characterization, molecular modeling, and potential antimicrobial and anticancer activities of novel 2-aminoisoindoline-1,3-dione derivatives.
abstract: In an effort to establish new drug candidates with improved antimicrobial and anticancer activities, we report here synthesis, molecular modeling, and in vitro biological evaluation of novel substituted N-amino phthalamide derivatives (3a-b, 4a-b, 5a-j, and 6). Structures of the newly synthesized compounds were described by IR, (1)H &(13)CNMR and LC-MS spectral data. The novel compounds were evaluated for their antibacterial activity against four types of Gm+ve and two for Gm-ve types, and antifungal activity against three fungi microorganisms by well diffusion method. Of these novel compounds, Schiff bases showed mostly promising antibacterial activity compared to reference drugs. A successful step was done for explanation of their mode of action through molecular docking of most active molecules at DNA gyrase B enzyme and further were biologically tested. Moreover, the antiproliferative activity was tested against two human carcinoma cell lines (Human colon carcinoma (HCT-116) and human breast adenocarcinoma (MCF-7)) showing promising anticancer activity compared to doxorubicin drug. The data from structure-activity relationship (SAR) analysis revealed that the lypophilic properties of these compounds might be essential parameter for their activity and suggest that 2-amino phthalamide scaffold derivatives 5g and 5h exhibited good antimicrobial and anticancer activities and might used as leads for further optimization.
authors.affiliation: Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, P.O. Box 30039, Al-Madinha Al-Munawaraha 41477, Saudi Arabia; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, P.O. Box 11651, Cairo 11884, Egypt. Electronic address: jan_25_misr@yahoo.com.
authors.forename: Hany Emary Ali
authors.initials: HE
authors.lastname: Ahmed
authors.affiliation: Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, P.O. Box 30039, Al-Madinha Al-Munawaraha 41477, Saudi Arabia; Department of Microbiology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt.
authors.forename: Hassan A
authors.initials: HA
authors.lastname: Abdel-Salam
authors.affiliation: Pharmaceutics and Pharmaceutical Technology Department, College of Pharmacy, Taibah University, P.O. Box 30039, Al-Madinha Al-Munawaraha 41477, Saudi Arabia; Department of Pharmaceutics, Faculty of Pharmacy, Helwan University, P.O. Box 11795, Cairo, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Shaker
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005658:Fungi / Q000187:drug effects*; D045325:HCT116 Cells; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D010797:Phthalimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000619894:2-((3,5-dibromo-2-hydroxybenzylidene)amino)isoindoline-1,3-dione; C000619911:2-((3-ethoxy-4-hydroxybenzylidene)amino)isoindoline-1,3-dione; D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D006835:Hydrazones; D010797:Phthalimides
keywords: 2-Aminoisoindoline-1,3-dione; Anticancer activity; Sciff base; Structure-selectivity relationships