title: An Eco-Friendly Ultrasound-Assisted Synthesis of Novel Fluorinated Pyridinium Salts-Based Hydrazones and Antimicrobial and Antitumor Screening.
abstract: The present work reports an efficient synthesis of fluorinated pyridinium salts-based hydrazones under both conventional and eco-friendly ultrasound procedures. The synthetic approach first involves the preparation of halogenated pyridinium salts through the condensation of isonicotinic acid hydrazide (1) with p-fluorobenzaldehyde (2) followed by the nucleophilic alkylation of the resulting N-(4-fluorobenzylidene)isonicotinohydrazide (3) with a different alkyl iodide. The iodide counteranion of 5-10 was subjected to an anion exchange metathesis reaction in the presence of an excess of the appropriate metal salts to afford a new series of fluorinated pyridinium salts tethering a hydrazone linkage 11-40. Ultrasound irradiation led to higher yields in considerably less time than the conventional methods. The newly synthesized ILs were well-characterized with FT-IR, ¹H NMR, (13)C NMR, (11)B, (19)F, (31)P and mass spectral analyses. The ILs were also screened for their antimicrobial and antitumor activities. Within the series, the salts tethering fluorinated counter anions 11-13, 21-23, 31-33 and 36-38 were found to be more potent against all bacterial and fungal strains at MIC 4-8 µg/mL. The in vitro antiproliferative activity was also investigated against four tumor cell lines (human ductal breast epithelial tumor T47D, human breast adenocarcinoma MCF-7, human epithelial carcinoma HeLa and human epithelial colorectal adenocarcinoma Caco-2) using the MTT assay, which revealed that promising antitumor activity was exhibited by compounds 5, 12 and 14.
authors.affiliation: Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia. nadjetrezki@yahoo.fr.|Department of Chemistry, Faculty of Sciences, University of Sciences and Technology Mohamed Boudiaf, Laboratoire de Chimie and Electrochimie des Complexes Metalliques (LCECM) USTO-MB, P.O. Box 1505, El M`nouar, Oran 31000, Algeria. nadjetrezki@yahoo.fr.
authors.forename: Nadjet
authors.initials: N
authors.lastname: Rezki
authors.affiliation: Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia. s7l_88@hotmail.com.
authors.forename: Salsabeel A
authors.initials: SA
authors.lastname: Al-Sodies
authors.affiliation: Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia. aouadmohamedreda@yahoo.fr.|Department of Chemistry, Faculty of Sciences, University of Sciences and Technology Mohamed Boudiaf, Laboratoire de Chimie and Electrochimie des Complexes Metalliques (LCECM) USTO-MB, P.O. Box 1505, El M`nouar, Oran 31000, Algeria. aouadmohamedreda@yahoo.fr.
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Aouad
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Jordan, Amman 11942, Jordan. S.Bardaweel@ju.edu.jo.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Bardaweel
authors.affiliation: Department of Chemistry, Faculty of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia. aboutasnim@yahoo.fr.
authors.forename: Mouslim
authors.initials: M
authors.lastname: Messali
authors.affiliation: Chemistry Department, Faculty of Science, Alexandria University, Alexandria 21500, Egypt. eelashry60@hotmail.com.
authors.forename: El Sayed H
authors.initials: el SH
authors.lastname: El Ashry
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005658:Fungi / Q000187:drug effects; D054879:Halogenation; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D061986:MCF-7 Cells; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011726:Pyridinium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012492:Salts / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000069453:Ultrasonic Waves
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D006835:Hydrazones; D011726:Pyridinium Compounds; D012492:Salts
keywords: anticancer activity; antimicrobial activity; hydrazones; metathesis; ultrasound irradiation