Synthesis, pharmacological evaluation and docking studies of N-(benzo[d]thiazol-2-yl)-2-(piperazin-1-yl)acetamide analogs as COX-2 inhibitors.
The existing NSAIDs having number of toxicities emphasises the need for discovery of new non-toxic anti-inflammatory agents. In this Letter, we present the simple two step chemical synthesis, in vivo pharmacological screening and docking study of few N-(benzo[d]thiazol-2-yl)-2-(piperazin-1-yl)acetamide analogs. Different amino benzothiazoles were chloroacetylated and further reacted with substituted piperazines in presence of a base to get N-(benzo[d]thiazol-2-yl)-2-(piperazin-1-yl)acetamide analogs (A1-C4). These compounds were evaluated for anti-inflammatory activity by carragenan induced paw oedema method. Promising compounds were screened for toxicity by evaluating the ulcerogenic potential. Molecular docking experiments were carried out against COX-2 enzyme using Surflex-Dock GeomX programme of Sybyl software on Dell T-1500 workstation to confirm the mechanism of action of active compounds among the series. In silico study reveal the binding interactions of N-(benzo[d]thiazol-2-yl)-2-(piperazin-1-yl)acetamide analogs with COX-2 protein and is in agreement with the in vivo anti-inflammatory activity.
Department of Pharmaceutical Chemistry, Gokaraju Rangaraju College of Pharmacy, Osmania University, Hyderabad 500 090, Andhra Pradesh, India. nmraghava@yahoo.in
Nulgumnalli Manjunathaiah
NM
Raghavendra
Aitha
A
Jyothsna
Alapati
A
Venkateswara Rao
C V S
CV
Subrahmanyam
D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism
D000081:Acetamides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052160:Benzothiazoles; D052246:Cyclooxygenase 2 Inhibitors; D051546:Cyclooxygenase 2