In vivo glucose-6-phosphatase inhibitory, toxicity and antidiabetic potentials of 2-picolylamine thioureas in Swiss albino mice

Abstract

The 2-picolylamine is a simplest analogue of the alkaloid that has secondary and tertiary nitrogen function in its cyclic structure like that of alkaloids that can be derivatized to a number of biologically active compounds. In connection to our previous work, in the present work, three thiourea derivatives ( I = 1,3- bis (2-benzyl-3-phenyl-1-(pyridine-2-yl) propyl) thiourea, II = 1,3-bis (pyridin-2-ylmethyl) thiourea, and III = 1-(2-benzyl-3-phenyl-1-(pyridine-2-yl) propyl)-3-phenylthiourea) were synthesized using 2-picolylamine template which is a readily available synthetic analogue of naturally occurring alkaloid. The biological effect of the synthesized derivatives were monitored on the activity of glucose-6-phosphatase in Swiss albino mice (21-days). The derivatives were also tested for their potential toxicity in a 28-days sub-chronic toxicity studies by assessing their effects on different parameters like hematological, serum biochemistry and liver histology. The therapeutic effect of the safe derivative ( I ) was examined in streptozotocin-induced diabetic mice as well. The derivatives showed inhibition of the enzyme activity from good to an excellent degree. Compound I had the highest inhibition with 21.42 ± 5.113 mg of the released phosphate as compared to that of the positive control group (84.55 ± 3.213 mg). Only I turned out to be safe for use in animals without exerting any toxic or lethal effects on any of the assessed parameters in the used animal model. Compound I efficiently reversed the effects like hyperglycemia, hyperlipidemia and weight loss in the test animals. Out of these three-tested compounds, I was found safe to be use as therapeutic agent in diabetes complications. However, further toxicological studies in other animal models are needed as well.

New N-acyl Thiourea Derivatives: Synthesis, Standardized Quantification Method and In Vitro Evaluation of Potential Biological Activities

“…Thiourea derivatives have been reported in the literature for their multiple biological activities, including antibacterial [1][2][3][4], antifungal [5,6], antitubercular [7][8][9], anthelmintic [10], antiviral [11,12], anticancer [4,13,14], analgesic [15][16][17], anti-inflammatory [1,18], anti-diabetic [19,20], anticonvulsant [21], antithyroid [22,23], antioxidant [24], insecticidal [25], herbicidal [26], and rodenticidal [27] effects. Thiourea derivatives are also versatile intermediates for the synthesis of heterocyclic compounds such as 1,3-thiazoles, pyrimidines, 1,2,4-triazines and 1,3-quinazolines [28].…”