Synthesis of acridinyl-thiazolino derivatives and their evaluation for anti-inflammatory, analgesic and kinase inhibition activities.
Variety of N-(4-phenyl-3-(2',3',4'(un)substituted phenyl)thiazol-2(3H)-ylidene)-2,4(un)substituted acridin-9-amine (4a-o) and 1-[(2,4-(un)substituted acridin-9-yl)-3-(4-phenyl-3-(2',3',4'(un)substituted phenyl)thiazol-2(3H)-ylidene)]isothiourea (5a-h) derivatives have been synthesized by condensation of 4-phenyl-3-(2',3',4'(un)substituted phenyl)thiazol-2(3H)-imine (3a-g) with 9-chloro-2,4-(un)substituted acridine (1a-c) and 9-isothiocyanato-2,4-(un)substituted acridine (2a-d), respectively. All these compounds were characterized by correct 1H NMR, FT-IR, MS and elemental analyses. These compounds were screened for anti-inflammatory, analgesic and kinase (CDK1, CDK5 and GSK3) inhibition activities. Some compounds exhibited good anti-inflammatory (25-32%) and potent analgesic (50-75%) activities, at 50 mg/kg p.o. A compound, 4o (R1 = H, R2 = OCH3, R3 = CH3, R4 = CH3, R5 = H) exhibited moderate CDK1 (IC50 = 8.5 microM) inhibition activity.
Sondhi
Sham M
SM
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee 247 667, India. sondifcy@iitr.ernet.in
Singh
Nirupma
N
Lahoti
Anand M
AM
Bajaj
Kiran
K
Kumar
Ashok
A
Lozach
Olivier
O
Meijer
Laurent
L
D000166:Acridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016227:Benzoquinones / Q000633:toxicity; D001921:Brain / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002351:Carrageenan / Q000633:toxicity; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D013552:Swine; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000166:Acridines; D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D004791:Enzyme Inhibitors; D013844:Thiazoles; C029322:phenylbenzoquinone; D002351:Carrageenan; D051360:Cyclin-Dependent Kinase 5; D016203:CDC2 Protein Kinase; C495906:Cdk5 protein, mouse; C495907:Cdk5 protein, rat; D018844:Cyclin-Dependent Kinases; D038362:Glycogen Synthase Kinase 3