Synthesis and hypoglycemic activity of some new theophylline derivatives.

Thirty-one new theophylline derivatives have been synthesized and evaluated for their hypoglycemic activity. Compounds 24 (56% reduction) and 31 (57% reduction) showed better hypoglycemic activity than the standard drug glibenclamide which showed 52% reduction in serum glucose level. Compound 27 remarkably reduced serum glucose level by 53%. Ten compounds showed varying degrees of hypoglycemic activity ranging from 20 to 37% reduction in serum glucose level compared to the standard drug. The aromatic amide functionality is the common feature of these theophylline hypoglycemic derivatives. However, anthranilamide and or aliphatic amides proved to be the least active compounds in the present series.

Drug-induced pulmonary fibrosis.

Pulmonary fibrosis is characterized by the accumulation of excessive connective tissue in the lungs. Its causes include chronic administration of some drugs for example bleomycin, cyclophosphamide, amiodarone, procainamide, penicillamine, gold and nitrofurantoin; exposure to certain environmental factors such as gases, asbestos and silica and bacterial or fungal infections. Some systemic diseases also predispose to the disease for example rheumatoid arthritis and systemic lupus erythematosus. The disease is associated with release of oxygen radicals and some mediators such as tumor necrosis factor-alpha TNF-alpha, transforming growth factor-beta TGF-beta, PDGF, IGF-I, ET-I and interleukins 1, 4, 8 and 13. The symptoms of the disease include dyspnea, non-productive cough, fever and damage to the lung cells. It is diagnosed with the aid of chest radiography, high resolution computed tomographic scanning and the result of pulmonary function tests. Drug-induced pulmonary fibrosis may involve release of free oxygen radicals and various cytokines for example IL-Ibeta and TNF-alpha via activation of nuclear transcription factor NF-beta as in the case of bleomycin and mitomycin or via release of TGF-beta as in case of tamoxifen or via inhibition of macrophages' and lymphocytes' phospholipases as in the case of amiodarone with the resultant accumulation of phospholipids and reduction of the immune system.

New flavane gallates isolated from the leaves of Plicosepalus curviflorus and their hypoglycemic activity.

Two new flavane gallates were isolated from the leaves of Plicosepalus curviflorus. The structure of the new compounds was established as 2S,3R-3,3',4',5,7-pentahydroxyflavane-5-O-gallate (1) and 2S,3R-3,3',4',5,5',7-hexahydroxyflavane-4',5-di-O-gallate (2), respectively. In addition, seven known compounds (-)-catechin (3), quercetin (4), lupeol (5), ß-sitosterol (6), pomolic acid (7), ß-sitosterol 3-O-ß-d-glucopyranoside (8) and 4-methoxycinnamic acid (9) were reported for the first time from the genus Plicosepalus. Compounds 1, 2 and 3 were investigated for their hypoglycemic activity and showed significant hypoglycemic activity in Swiss Albino mice.

Synthesis, analgesic and anti-inflammatory evaluation of some novel quinazoline derivatives.

Two series of some new 2,4,6-trisubstituted-quinazoline derivatives were prepared and screened for their analgesic, anti-inflammatory activity and acute toxicity. Four compounds were more potent analgesic agents than the reference drug Indomethacin and thirteen compounds showed significant anti-inflammatory activity. Seven compounds showed combined ability to inhibit both pain and inflammation. Compounds tested for acute toxicity showed no toxic symptoms or mortality rates 24 h post-administration implying their good safety margin.