title: Pharmacological and structure-activity relationship evaluation of 4-aryl-1-diphenylacetyl(thio)semicarbazides.
abstract: This article describes the synthesis of six 4-aryl-(thio)semicarbazides (series a and b) linked with diphenylacetyl moiety along with their pharmacological evaluation on the central nervous system in mice and computational studies, including conformational analysis and electrostatic properties. All thiosemicarbazides (series b) were found to exhibit strong antinociceptive activity in the behavioural model. Among them, compound 1-diphenylacetyl-4-(4-methylphenyl)thiosemicarbazide 1b was found to be the most potent analgesic agent, whose activity is connected with the opioid system. For compounds from series a significant anti-serotonergic effect, especially for compound 1-diphenylacetyl-4-(4-methoxyphenyl)semicarbazide 2b was observed. The computational studies strongly support the obtained results.
authors.affiliation: Department of Organic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland. monika.wujec@umlub.pl.
authors.forename: Monika
authors.initials: M
authors.lastname: Wujec
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Chodźki 4a, 20-093 Lublin, Poland. ewa.kedzierska@umlub.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Kędzierska
authors.affiliation: Department of Organic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland. edyta.kusmierz@umlub.pl.
authors.forename: Edyta
authors.initials: E
authors.lastname: Kuśmierz
authors.affiliation: Department of Organic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland. tomasz.plech@umlub.pl.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Plech
authors.affiliation: History of Medical Sciences Department, Medical University, Szkolna 18, 20-124 Lublin, Poland. wand@bg.umlub.pl.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wróbel
authors.affiliation: Department of Organic Chemistry, Medical University, Chodźki 4a, 20-093 Lublin, Poland. piotr.paneth@p.lodz.pl.
authors.forename: Agata
authors.initials: A
authors.lastname: Paneth
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Chodźki 4a, 20-093 Lublin, Poland. jolanta.orzelska@umlub.pl.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Orzelska
authors.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Chodźki 4a, 20-093 Lublin, Poland. sylwia.fidecka@umlub.pl.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Fidecka
authors.affiliation: Institute of Applied Radiation Chemistry, Technical University of Lodz, Zeromskiego 116, 90-924 Lodz, Poland. piotr.paneth@p.lodz.pl.
authors.forename: Piotr
authors.initials: P
authors.lastname: Paneth
mesh_terms: D019342:Acetic Acid; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D012663:Semicarbazides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000927:Anticonvulsants; D012663:Semicarbazides; D012702:Serotonin Antagonists; D019342:Acetic Acid; D010433:Pentylenetetrazole
references.citation: Neuropsychopharmacology. 1991 May;4(3):187-97
references.pmid: 2064718
references.citation: J Am Chem Soc. 1988 Mar 1;110(6):1657-66
references.pmid: 27557051
references.citation: Eur J Med Chem. 2011 Jan;46(1):241-8
references.pmid: 21130541
references.citation: Psychopharmacology (Berl). 2004 May;173(3-4):270-7
references.pmid: 14740148
references.citation: Eur J Med Chem. 2011 Nov;46(11):5616-24
references.pmid: 21993152
references.citation: Eur J Med Chem. 2010 Aug;45(8):3365-73
references.pmid: 20510483
references.citation: Psychopharmacologia. 1967;11(1):65-78
references.pmid: 5302272
references.citation: J Mol Model. 2011 Sep;17(9):2297-303
references.pmid: 21080016
references.citation: Pharmacol Biochem Behav. 1995 Jun-Jul;51(2-3):245-7
references.pmid: 7667335
references.citation: J Clin Microbiol. 2003 Jun;41(6):2596-604
references.pmid: 12791886
references.citation: Eur J Med Chem. 2011 Nov;46(11):5717-26
references.pmid: 21978836
references.citation: Science. 1981 May 15;212(4496):827-9
references.pmid: 7221567
references.citation: J Med Chem. 2001 Apr 26;44(9):1475-8
references.pmid: 11311072
references.citation: Eur J Pharm Sci. 1999 Oct;9(1):25-31
references.pmid: 10493993
references.citation: Br J Pharmacol. 1985 Mar;84(3):743-53
references.pmid: 2580582
references.citation: Schweiz Med Wochenschr. 1955 Mar 26;85(13):305-9
references.pmid: 14372907
references.citation: Eur J Med Chem. 2004 Oct;39(10):849-53
references.pmid: 15464618
references.citation: J Pharmacol Exp Ther. 1949 Jun;96(2):99-113
references.pmid: 18152921
references.citation: Br J Pharmacol Chemother. 1963 Feb;20:106-20
references.pmid: 14023050
references.citation: J Mol Model. 2012 Mar;18(3):843-9
references.pmid: 21625902
references.citation: Pharmacol Biochem Behav. 1990 Aug;36(4):901-6
references.pmid: 2145593
references.citation: Psychopharmacology (Berl). 1986;88(3):320-4
references.pmid: 2870532
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2014 Apr;387(4):367-75
references.pmid: 24326964
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1982 Dec;321(4):265-70
references.pmid: 6132341
references.citation: Farmaco. 2004 Oct;59(10):775-83
references.pmid: 15474054
references.citation: Farmaco. 2005 Jan;60(1):1-5
references.pmid: 15652361
references.citation: Farmaco. 2002 Mar;57(3):253-7
references.pmid: 11989804
references.citation: Neuropharmacology. 1996;35(8):1101-7
references.pmid: 9121613
references.citation: Eur J Med Chem. 2011 Apr;46(4):1415-24
references.pmid: 21316819
references.citation: Bioorg Med Chem. 2002 Mar;10(3):501-6
references.pmid: 11814835
references.citation: J Pharmacol Exp Ther. 1984 Jan;228(1):133-9
references.pmid: 6694097
references.citation: J Pharmacol Exp Ther. 1992 Aug;262(2):692-8
references.pmid: 1501117
references.citation: Bioorg Med Chem. 2008 Oct 1;16(19):8976-87
references.pmid: 18804379
references.citation: Eur J Med Chem. 2004 Jun;39(6):535-45
references.pmid: 15183912
references.citation: Eur J Pharmacol. 1990 Sep 4;186(1):115-8
references.pmid: 2282932
references.citation: Med Chem. 2010 Jan;6(1):44-50
references.pmid: 20402660
references.citation: Eur J Med Chem. 2011 Sep;46(9):4702-8
references.pmid: 21816517