title: Synthesis, biological evaluation and molecular modeling of novel series of pyridine derivatives as anticancer, anti-inflammatory and analgesic agents.
abstract: This paper presents a combined synthesis; characterization, computational and biological activity studies of novel series of pyridines heterocyclic compounds. The compounds have been characterized by elemental analyses and spectral like IR, (1)H NMR, (13)C NMR and MS studies. Michael addition of substituted-2-methoxycarbonylacetanilide 2a,b on the α-substituted cinnamonitriles 3a-d gave the corresponding 2-pyridone derivatives 5-10. Structures of the titled compounds cited in this article were elucidated by spectrometric data (IR, (1)H NMR, (13)C NMR and MS). The molecular modeling of the synthesized compounds has been drawn and their molecular parameters were calculated. Also, valuable information is obtained from the calculation of molecular parameters including electronegativity, net dipole moment of the compounds, total energy, electronic energy, binding energy, HOMO and LUMO energy. Various in vitro antitumor as well as in vivo anti-inflammatory and analgesic activities of the synthesized compounds were investigated. Evaluation of anti-inflammatory activity of test compounds was performed using carrageenan induced paw edema in rats. All the tested compounds showed moderate to good activity. The SAR results indicate that all compounds showed moderate to good activity, among these 7 and 10 compounds having -N(CH3)2 group are most effective.
authors.affiliation: Department of Chemistry, Faculty of Science, Al-Azhar University, 11284 Nasr City, Cairo, Egypt; Department of Chemistry, Faculty of Arts and Science, Northern Border University, Rafha, Saudi Arabia.
authors.forename: M H
authors.initials: MH
authors.lastname: Helal
authors.affiliation: Pharmacology Department, National Research Center, El-Bohoth St., Dokki, P.O. 12622, Cairo, Egypt.
authors.forename: S A
authors.initials: SA
authors.lastname: El-Awdan
authors.affiliation: Department of Chemistry, Faculty of Science, Al-Azhar University, 11284 Nasr City, Cairo, Egypt; Department of Chemistry, Faculty of Science and Arts, King Khalid University, Mohail Assir, Saudi Arabia.
authors.forename: M A
authors.initials: MA
authors.lastname: Salem
authors.affiliation: Department of Chemistry, Faculty of Science, Al-Azhar University, 11284 Nasr City, Cairo, Egypt.
authors.forename: T A
authors.initials: TA
authors.lastname: Abd-elaziz
authors.affiliation: Department of Chemistry, Faculty of Science, Al-Azhar University, 11284 Nasr City, Cairo, Egypt.
authors.forename: Y A
authors.initials: YA
authors.lastname: Moahamed
authors.affiliation: Department of Chemistry, Faculty of Arts and Science, Northern Border University, Rafha, Saudi Arabia; Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt. Electronic address: aelsherif72@yahoo.com.
authors.forename: A A
authors.initials: AA
authors.lastname: El-Sherif
authors.affiliation: Department of Chemistry, Faculty of Science, Al-Azhar University, 11284 Nasr City, Cairo, Egypt.
authors.forename: G A M
authors.initials: GA
authors.lastname: Mohamed
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D011725:Pyridines; C023666:pyridine
keywords: Analgesic; Anti-inflammatory; Anticancer; Micheal addition; Pyridones; SAR