ABSTRACT
A facile, convenient and high yielding synthesis of novel thioglycosides incorporating 1,3,4-oxadiazole, triazole and or triazine moieties from readily available starting materials has been described. The key step of this protocol is the formation of 3-isobutyl-1-phenyl-1H-pyrazole-4-carbaldehyde (3) via condensation between methyl iso-butyl ketone and phenylhydrazine followed by application of Vilsmeier-Haack reaction. 3 was converted either to 1,3,4-oxadiazole derivative or condensed with O-aminothiols to give the bases 8, 19 and 20 in good yields, respectively. The aglycons 8, 19, and 20 were coupled with different activated halosugars in the presence of basic medium. Pharmacological evaluation of compounds 8, 14, 16 and 22 in vitro against 2-cell lines MCF-7 (breast) and HEPG2 (liver) revealed them to possess high anti-tumor activities with IC(50) values ranging from 2.67-20.25 (µg/mL) for breast cell line (MCF-7) and 4.62-43.6 (µg/mL) for liver cell line (HEPG2). None of the tested compounds exhibited any toxicity in doses up to 500 mg kg(-1) of the animal body weight.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Drug Design , Oxadiazoles/chemistry , Oxadiazoles/pharmacology , Thioglycosides/chemistry , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/toxicity , Cell Line, Tumor , Humans , Inhibitory Concentration 50 , Male , Oxadiazoles/chemical synthesis , Oxadiazoles/toxicity , Rats , Rats, WistarABSTRACT
Chalcone derivative 3 was synthesized via the base catalyzed Claisen-Schmidt condensation and was used as a precursor for synthesizing pyrazoline 11, isoxazoline 12, pyrazoline carbothioamide 13, 5,6-dihydropyrimidine-2-(1H)-thione 14 and aminopyridinecarbonitrile derivative 15. Bromination of 3 afforded the dibromo derivative 4. Monobromo derivative 5 obtained by boiling 4 in dry benzene in the presence of triethylamine. Fused thiadiazines 9a,b and 1,4-thiazine 9c derivatives were synthesized upon treatment of α-bromopropenone derivative 5 with 4-amino-4H-1,2,4-triazole-3-thiol (6) or 1-amino-2-mercapto-5-methylpyrimidin-4(1H)-one (7) or with 2-aminothiophenol (8) in ethanolic potassium hydroxide solution. The newly synthesized compounds were screened for their molluscicidal activities, whereas compounds 3, 4, 9a, 11 and 15 exhibited promising molluscicidal activities. On the other hand compounds 5, 9b, 9c, 12, 13 and 14 showed a moderate effect as compared to the standard molluscicidal agent (Bayluscide).
Subject(s)
Mollusca/drug effects , Molluscacides/chemical synthesis , Molluscacides/pharmacology , Animals , Isoxazoles/chemistry , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molluscacides/chemistry , Pyrazoles/chemistry , Pyridines/chemistry , Pyrimidines/chemistry , Thiadiazines/chemistry , Thiazines/chemistryABSTRACT
A series of fused and non fused 1,2,4-triazoles with (2,4-dichlorophenoxy) moiety are prepared utilizing 3-((2,4-dichlorophenoxy)methyl)-4-amino-4H-1,2,4-triazole-5-thiol (3). The latter on reaction with carboxylic acids, ethylchloroformate, ethylcyanoacetate and sodium nitrite gives five membered fused triazole derivatives 4a-d, 5, 6, 7 and 10, respectively. The six membered heterocycles 11, 12 and 14 are prepared by cyclization of compound 3 with phenacyl bromide, chloroacetic acid and alpha-bromoketone respectively. Most of the newly synthesized compounds were screened for their anti-inflammatory and molluscicidal activities. The compounds 4b, 4d, 11 and 14 showed potent anti-inflammatory activities in dose dependent manner while compounds 3, 4b, 8 and 10 exhibited promising molluscicidal activities.