Synthesis and pharmacological evaluation of antiinflammatory mutual amide prodrugs.

Nonsteroidal antiinflammatory drugs have been widely used for the management of inflammation, pain and nociception. Gastric intolerance caused by most of the nonsteroidal antiinflammatory drugs used today restricts their use. Several approaches have been proposed to modify the parent nonsteroidal antiinflammatory drugs molecule in order to reduce their gastric toxicity. Oral prodrug approach is one of such approaches. In the present work three nonsteroidal antiinflammatory drugs viz. ibuprofen, diclofenac, and flurbiprofen were conjugated with sulfonamides like sulphamethoxazole and sulphanilamide via amide bond using dicyclohexylcarbodiimide coupling reaction. The synthesized prodrugs were screened for their analgesic and antiinflammatory activity using Eddy's hot plate, acetic acid-induced writhing and carrageenan-induced rat paw edema method, respectively. These prodrugs were also evaluated for their ulcerogenic potential. All synthesized prodrugs were found to be less ulcerogenic than their parent nonsteroidal antiinflammatory drugs and showed better activity profile in terms of analgesic and antiinflammatory activity as compared to their respective parent drugs.

Targeting angiogenesis for treatment of human cancer.

Recent advances in cancer research highlighted the importance of target-specific drug discovery. In view of these advances, the most important mechanism in tumour growth is its ability to stimulate the formation of blood capillaries around itself called tumour-driven angiogenesis. Hence targeting the angiogenesis, inhibits the growth of blood vessels around it and responsible for death of the tumour due to starvation and accumulation of toxic waste. The therapy, thus, indirectly cytotoxic to the tumour cells by targeting newly developing blood vessels. In this review, we summarised the various antiangiogenic agents with their clinical uses and current status.

Synthesis and evaluation of antiinflammatory, analgesic and ulcerogenic potential of NSAIDs bearing 1,3,4-oxadiazole scaffold.

Synthesis of 1,3,4-oxadiazole derivatives of diclofenac and mefenamic acid are described. The target compounds 5-[2-(2,6-dichloroanilino)benzyl]-2-aryl-1,3,4-oxadiazole (3a-3e) and 5-[2-(2,3-dimethylanilino)phenyl]-2-(aryl)-1,3,4-oxadiazole (6a-6e) were obtained by treating 2 and 5 with various aromatic acids using POCl(3) as dehydrating agent. They were purified and characterized by IR, (1)H-NMR and elemental analysis. These compounds were further subjected to antiinflammatory, analgesic and acute ulcerogenic activity. Compound 3c and 6d exhibited good antiinflammatory activity and compounds 3c, 3e, 6c, 6d, 6e were found to be non ulcerogenic.

HDAC inhibitors - new generation of target specific treatment.

Histone Deacetylases (HDACs) enzymes are critical in regulating gene expression and transcription. They also play a fundamental role in regulating cellular activities such as cell proliferation, survival and differentiation. Inhibition of HDACs has generated many fascinating results including a new strategy in human cancer therapy. HDAC Inhibitors (HDACIs) like SAHA, TSA are emerging as new promising drugs for various anti-inflammatory and CNS-disorders. This review, along with chemical classification, emphasizes on the therapeutic potential of various HDACIs against different diseases.