title: Synthesis, Antimicrobial and Hypoglycemic Activities of Novel N-(1-Adamantyl)carbothioamide Derivatives.
abstract: The reaction of 1-adamantyl isothiocyanate 4 with the various cyclic secondary amines yielded the corresponding N-(1-adamantyl)carbothioamides 5a-e, 6, 7, 8a-c and 9. Similarly, the reaction of 4 with piperazine and trans-2,5-dimethylpiperazine in 2:1 molar ratio yielded the corresponding N,N'-bis(1-adamantyl)piperazine-1,4-dicarbothioamides 10a and 10b, respectively. The reaction of N-(1-adamantyl)-4-ethoxycarbonylpiperidine-1-carbothioamide 8c with excess hydrazine hydrate yielded the target carbohydrazide 11, in addition to 4-(1-adamantyl)thiosemicarbazide 12 as a minor product. The reaction of the carbohydrazide 11 with methyl or phenyl isothiocyanate followed by heating in aqueous sodium hydroxide yielded the 1,2,4-triazole analogues 14a and 14b. The reaction of the carbohydrazide 11 with various aromatic aldehydes yielded the corresponding N'-arylideneamino derivatives 15a-g. The compounds 5a-e, 6, 7, 8a-c, 9, 10a, 10b, 14a, 14b and 15a-g were tested for in vitro antimicrobial activity against certain strains of pathogenic Gram-positive and Gram-negative bacteria and the yeast-like fungus Candida albicans. The compounds 5c, 5d, 5e, 6, 7, 10a, 10b, 15a, 15f and 15g showed potent antibacterial activity against one or more of the tested microorganisms. The oral hypoglycemic activity of compounds 5c, 6, 8b, 9, 14a and 15b was determined in streptozotocin (STZ)-induced diabetic rats. Compound 5c produced significant reduction of serum glucose levels, compared to gliclazide.
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. ealabdullah@ksu.edu.sa.
authors.forename: Ebtehal S
authors.initials: ES
authors.lastname: Al-Abdullah
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. haltuwajri@ksu.edu.sa.
authors.forename: Hanaa M
authors.initials: HM
authors.lastname: Al-Tuwaijri
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia. hananhafila@hotmail.com.
authors.forename: Hanan M
authors.initials: HM
authors.lastname: Hassan
authors.affiliation: Department of Chemistry, College of Sciences, King Saud University, Riyadh 11451, Saudi Arabia. mshaikh@ksu.edu.sa.
authors.forename: Monirah A
authors.initials: MA
authors.lastname: Al-Alshaikh
authors.affiliation: Department of Microbiology, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt. sayedhabib@hotmail.co.jp.|Department of Pharmaceutics and Pharmaceutical Technology (Microbiology), College of Pharmacy, Taibah University, Almadinah Almunawwarah 11344, Saudi Arabia. sayedhabib@hotmail.co.jp.
authors.forename: Elsayed E
authors.initials: EE
authors.lastname: Habib
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia. aelemam@ksu.edu.sa.
authors.forename: Ali A
authors.initials: AA
authors.lastname: El-Emam
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006834:Hydrazines / Q000737:chemistry / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017879:Isothiocyanates / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D006834:Hydrazines; D007004:Hypoglycemic Agents; D017879:Isothiocyanates; D014230:Triazoles; C571392:adamantyl isothiocyanate; C029424:hydrazine; C045575:1,2,4-triazole; D000218:Adamantane; C019289:carbohydrazide