[Show abstract][Hide abstract] ABSTRACT: Lipophilic drugs have limited solubility in phospholipid systems, hence maximum entrapment levels in liposomes are known to be low. Barbigerone (Bar), an anti-cancer isoflavone, is water insoluble and an effective delivery route is through encapsulation in cyclodextrins (CDs) followed by a second encapsulation in liposomes. In this study, Bar or its inclusion complex [Bar/2-hydroxypropyl-β-CD (HP-β-CD)] were incorporated into liposomes prepared by the ethanol injection method. A 4.6-fold increase of encapsulation efficiency was achieved for the liposome-Bar/HP-β-CD complex (Bar/HP-β-CD/liposome) in comparison with the conventional Bar/liposome. The size of the Bar/HP-β-CD/liposome was 87.76 ± 1.45 nm and the zeta potential was −35.02 ± 0.50 mV. In addition, the liposomes remained stable in liquid form at 4 °C for at least 3 months. The Bar/HP-β-CD/liposome was evaluated for anti-cancer activity in hepatocarcinoma HepG2 and colon cancer C26 cells and showed comparable toxicity to that of plain Bar. In vivo studies in hepatic cancer xenografted nude mice model showed that Bar/HP-β-CD/liposome significantly inhibited tumor growth with a substantial increase in animal survival. In conclusion, the encapsulation of the Bar/HP-β-CD complex into liposomes could provide an alternative means for its potential use in cancer therapy.
No preview · Article · May 2015 · Journal of inclusion phenomena and macrocyclic chemistry
[Show abstract][Hide abstract] ABSTRACT: A series of 4β-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin congeners were synthesized by employing click chemistry and further evaluated for their antitumor activity by MTT assay. Among them, six congeners (10, 11, 12, 13, 22, and 24) exhibited approximately 100-fold more potent inhibitory activity against four tumor cell lines (HepG2, MKN-45, NCI-H1993, and B16) than etoposide as positive control. Docking studies on binding in the ATPase domain of topoisomerase II revealed perfect docking of four congeners in the active site. Furthermore, the podophyllotoxin congeners 10, 11, 12, and 13 induced cell cycle arrest of HepG2 cells at the G(2) /M phase in a concentration-dependent manner, assessed by flow cytometric analysis, highlighting that they exert their antitumor activity via HepG2 cell apoptosis.
No preview · Article · Dec 2012 · Archiv der Pharmazie
[Show abstract][Hide abstract] ABSTRACT: Present studies have shown that the lipid carrier has a significant role in several aspects of metabolic syndrome in A-FABP/ap2-deficient mice, including type 2 diabetes and atherosclerosis. 38 Thiazole- and indole-based derivatives were synthesized and investigated for their inhibitory effects on the production of LPS-stimulated TNF-α. Among them, 12b exhibited an excellent inhibitory efficiency compared to BMS309403 (95% vs. 85%) at the concentration of 10 μM and a binding affinity for ap2 with the apparent K(i) values 33 nM. Oral administration of 12b at a dosage of 50 mg/kg effectively reduced the levels of plasma blood glucose, triglycerides, insulin, total cholesterol and alanine aminotransferase in high-fat/diet-induced obesity model. The results highlighted that 12b was a potent anti-diabetic agent.
No preview · Article · Mar 2012 · European Journal of Medicinal Chemistry
[Show abstract][Hide abstract] ABSTRACT: In this paper, we reported the synthesis of bifendate derivatives and evaluation of anti-inflammatory activity by detecting the production of the Nitric Oxide (NO) in the lipopolysaccharide(LPS)-stimulated RAW 264.7 cell lines. Among the newly derivatives, compound 7k was the most potent one and two other compounds (7e and 7f) also exhibited greater anti-inflammatory activity than bifendate. Further in vivo studies confirmed that 7k significantly and dose-dependently inhibited carrageenan-induced paw edema and decreased the serum levels of alanine aminotransaminase, and aspartate aminotransaminase in concanavalin A-induced hepatitis model. Histopathological evaluation demonstrated that 7k has better hepatoprotective effect on acute liver injury induced by concanavalin A than bifendate, suggesting that 7k is a potential drug candidate for the treatment of hepatic injuries.
No preview · Article · Dec 2011 · European Journal of Medicinal Chemistry
[Show abstract][Hide abstract] ABSTRACT: Twenty-two compounds based on thiazolidine-2,4-dione moiety were synthesized and evaluated for the inhibitory potency on the production of nitric oxide (NO), inducible nitric oxide synthase (iNOS) activity, and the generation of prostaglandin E(2) (PEG(2)). (Z)-N-(3-chlorophenyl)-2-(4-((2,4-dioxothiazolidin-5-ylidene) methyl) phenoxy) acetamide (3I), superior to the commercial anti-inflammatory drug indomethacin, significantly inhibited iNOS activity (IC(50) = 8.66 μM), iNOS-mediated NO, and cyclooxygenase (COX)-2-derived PGE(2) production (IC(50) = 4.16 and 23.55 μM, respectively) on lipopolysaccharide (LPS)-induced RAW 264.7 cells. Docking study revealed that 3I was perfectly docking into the active site of murine iNOS and suppressed the expression of iNOS protein as evidenced by Western blot analysis. At the dose of 50 mg/kg, oral administration of 3I possessed protective properties in both carrageenan-induced paw edema and adjuvant-induced arthritis rat models.
No preview · Article · Mar 2011 · Journal of Medicinal Chemistry
[Show abstract][Hide abstract] ABSTRACT: Forty-four barbituric acid or thiobarbituric acid derivatives were synthesized and evaluated for their effects on adipogenesis of 3T3-L1 adipocytes by measuring the expression of adiponectin in vitro. Four compounds (3a, 3o, 3s, 4t) were found to increase the expression of adiponectin and lower the leptin level in 3T3-L1 adipocytes at respective concentration of 10 μM. Among them, 3s showed the most efficacious. Oral administration of 3s effectively reduced body weight, liver weight, and visceral fat and regulated serum levels of biochemical markers in the high-fat/diet-induced Wistar rats. Histopathological evaluation of liver sections by Oil Red O and H&E staining confirmed 3s as a potent, orally active molecule for reducing fat deposition against non-alcoholic fatty liver disease.
No preview · Article · Feb 2011 · European Journal of Medicinal Chemistry