ABSTRACT
A series of novel isoxazolo[5',4':5,6]pyrido[2,3-b]indoles 7a-h were synthesized and tested for their in vitro and in vivo anticancer activities. The analogs 7d and 7g have shown potential anticancer activity as compared with the reference compound Cisplatin.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Indoles/chemical synthesis , Animals , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Cisplatin/pharmacology , Humans , Indoles/chemistry , Indoles/pharmacology , Inhibitory Concentration 50 , Isoxazoles/chemical synthesis , Isoxazoles/chemistry , Isoxazoles/pharmacology , Male , Mice , Molecular Structure , Pyridones/chemical synthesis , Pyridones/chemistry , Pyridones/pharmacologyABSTRACT
Novel series of 2-methyl-3-{3-methyl-5-[(E)-2-phenyl-1-ethenyl]-4-isoxazolyl}-3,4-dihydropyrimido[4,5-b]quinolin-4-ones 5 and 3-{3-methyl-5-[(E)-2-phenyl-1-ethenyl]-4-isoxazolyl}-3,4-dihydro-2H-chromeno[2,3-d]pyrimidin-4-ones 7 have been synthesized from isoxazolyl cyanoacetamide synthon 2. Compound 2 was obtained by reaction of 4-amino-3-methyl-5-styrylisoxazole 1 with ethyl cyanoacetate. Isoxazolyl pyrimido[4,5-b]quinolin-4-ones 5 were obtained from compounds 2 by condensation with o-nitro benzaldehyde followed by treatment with SnCl(2) and subsequent tandem N-acetylation and cyclodehydration with acetic anhydride. Compounds 2 were converted to isoxazolyl chromeno[2,3-d]pyrimidin-4-ones 7 by reaction with salicylaldehydes and subsequent cyclization with formaldehyde. Compounds 2-7 were characterized by IR, (1)H NMR, (13)C NMR, and Mass spectral data. The title compounds 5a-f and 7a-g were evaluated for their antimicrobial, anti-inflammatory and analgesic activity. Compounds 5d and 7e exhibited significant antimicrobial activity, potent anti-inflammatory and analgesic activities as that of standard drugs.
Subject(s)
Drug Design , Isoxazoles/chemistry , Pyrimidinones/chemical synthesis , Pyrimidinones/pharmacology , Quinolines/chemical synthesis , Quinolines/pharmacology , Analgesics/chemical synthesis , Analgesics/chemistry , Analgesics/pharmacology , Analgesics/therapeutic use , Animals , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/therapeutic use , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Bacteria/drug effects , Behavior, Animal/drug effects , Chemistry Techniques, Synthetic , Edema/drug therapy , Fungi/drug effects , Microbial Sensitivity Tests , Pyrimidinones/chemistry , Pyrimidinones/therapeutic use , Quinolines/chemistry , Quinolines/therapeutic use , RatsABSTRACT
A series of novel methylene bis-isoxazolo[4,5-b]azepines have been synthesized by reaction of 3,5-dimethyl-4-nitroisoxazole 6 with an appropriate methylene bis-chalcones 7 to obtain various Michael adducts 8a-i, which on treatment with SnCl(2)-MeOH underwent reductive cyclization to afford the title compounds 9a-i. Structure of these compounds were established on the basis of IR, (1)H NMR, (13)C NMR and mass spectral data. The title compounds 9a-i were evaluated for their in vitro antimicrobial and anticancer activities. Compounds 9h and 9i exhibited potent antimicrobial and anticancer activities as that of standard drugs.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Azepines/chemical synthesis , Azepines/pharmacology , Bacteria/drug effects , Breast Neoplasms/drug therapy , Drug Design , Isoxazoles/chemical synthesis , Isoxazoles/pharmacology , Cell Proliferation/drug effects , Cells, Cultured , Female , Humans , Kidney/cytology , Kidney/drug effects , Microbial Sensitivity Tests , Molecular Structure , Structure-Activity RelationshipABSTRACT
A series of novel phenylmethylene bis-isoxazolo[4,5-b]azepine derivatives (10) have been synthesized from 3-methyl-4-nitro-5-styrylisoxazoles 6. The reaction of 6 with 3,5-dimethyl-4-nitroisoxazole (7) in piperidine afforded the Michael type adducts 8, which on treatment with different substituted chalcones in the presence of piperidine gave the Michael adducts 9. Compounds 9 underwent reductive cyclization on treatment with SnCl(2)-MeOH to afford the title compounds 10. Structure of these compounds was established on the basis of IR, (1)H NMR, (13)C NMR and Mass spectral data. The title compounds 10a-j were evaluated for in vitro and in vivo anticancer activity. Compound 10j exhibited good anticancer activity as that of standard drug Cisplatin.
