Asperaldin, a new aldose reductase inhibitor from Aspergilus niger CFR-1046. I. Fermentation, isolation and characterization.

Aldose reductase (EC 1.1.1.21) catalyzes the conversion of glucose to sorbitol and promotes the accumulation of sorbitol in various tissues under the condition of hyperglycemia such as diabetes mellitus. The accumulated intracellular sorbitol causes development of diabetic complications such as cataracts, neuropathy, retinopathy and nephropathy1). Inhibitors of aldose reductase have been shown to reverse these biochemical changes and have been proven effective in delaying and even preventing several diabetic pathologies. Thus, aldose reductase has become an attractive pharmacological target for the treatment of diabetic complications. It has been reported that inhibitors of aldose reductase reduce the tissue sorbitol content in diabetic animals and are useful as therapeutic agents for diabetic complications2). In our screening programme on bioactive molecules through the fermentation route3-7), we screened 15 different strains of Aspergillus sp. for potential inhibitors against rat lens aldose reductase (RLAR). We found that, Aspergillus niger CFR-1046 produced a compound, termed by us as asperaldin, which exhibits potent inhibitory activity against RLAR. The present paper describes the fermentation, isolation, physico-chemical properties and biological activities of asperaldin. The organism used in this study Aspergillus niger CFR 1046 was obtained from CFTRI culture collection. Submerged fermentation was carried out in a potato dextrose (soluble starch 0.4% and glucose 2%) medium. A portion of the mature agar slant was inoculated into 100ml of potato dextrose broth in a 500ml Erlenmeyer flask and incubated at 30°C on a rotary shaker at 250rpm for 8 days.