Main Article Content
Protein glycation is one of the major causes of diabetic complications while antiglycation therapy is the most important intervention to manage diabetic complications. Currently, sulfur-containing compounds are under extensive studies due to their vast pharmacological applications particularly, against diabetic mellitus and oxidative stress induced pathological disorders.
Present study is an effort to evaluate various classes of organosulfur compounds to explore promising inhibitors against protein glycation with enhanced antiglycation potential and low toxic effects. A library of organosulfur compounds belonging to different classes was investigated for their potential inhibition against protein glycation in vitro while MTT assay on mouse fibroblast 3T3 cells was used to assess the potential cytotoxicity of most promising antiglycation agents.
On antiglycation assay, eight organosulfur compounds (1-8) exhibited a potent antiglycation activity with IC50 values (<16 µM), as compared to standard antiglycation agent rutin (IC50 = 98.01±2.03 µM). Similarly, compound (9) and compound (10) exhibited good antiglycation potential with IC50 values 591.6±1.53 and 401±1.20 µM, respectively. In this assay compounds (12-18) exhibited moderate antiglycation activity (47-62% inhibition) at 1mM concentration.
On mouse fibroblast 3T3 cells cytotoxicity assay, all the tested compounds were found to be largely non-toxic with IC50 values (72.5-100) µM. In this assay, compound (10) exhibited slight toxic nature with IC50 value 5.00±1.89 as compared cycloheximide which is used as a standard in this assay with IC50 value 0.3 ± 0.089 μM.
Key Words: Organosulfur compounds, diabetic complications, antiglycation agents, cytotoxicity assay
This work is licensed under a Creative Commons Attribution 4.0 International License.Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under aÂ Creative Commons Attribution LicenseÂ that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeÂ The Effect of Open Access).
1- Xi M, Hai C, Tang H, Chen M, Fang K, Liang X. Antioxidant and antiglycation properties of total saponins extracted from traditional Chinese medicine used to treat diabetes mellitus. Phytotherapy Research. 2008;22(2):228-37.
2- Bry L, Chen PC, Sacks DB. Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clinical Chemistry. 2001;47(2):153-63.
3- Graves DT, Liu R, Alikhani M, Al-Mashat H, Trackman PC. Diabetes-enhanced inflammation and apoptosis—impact on periodontal pathology. Journal of dental research. 2006;85(1):15-21.
4- Reddy VP, Beyaz A. Inhibitors of the Maillard reaction and AGE breakers as therapeutics for multiple diseases. Drug discovery today. 2006;11(13):646-54.
5- Singh R, Barden A, Mori T, Beilin L. Advanced glycation end-products: a review. Diabetologia. 2002;44(2):129-46.
6- Bendayan M. Immunocytochemical detection of advanced glycated end products in rat renal tissue as a function of age and diabetes. Kidney international. 1998;54(2):438-47.
7- 10- Wu CH, Huang SM, Lin JA, Yen GC. Inhibition of advanced glycation endproduct formation by foodstuffs. Food & function. 2011;2(5):224-34.
8- Choudhary MI, Basha FZ, Abbas G, Khan SN, Shah S. Science at the interface of chemistry and biology: Discoveries of α-glucosidase inhibitors and antiglycation agents. Pure and Applied Chemistry. 2007;79(12):2263-8.
9- Mosihuzzman M, Naheed S, Hareem S, Talib S, Abbas G, Khan SN, Choudhary MI, Sener B, Tareen RB, Israr M. Studies on α-glucosidase inhibition and anti-glycation potential of Iris loczyi and Iris unguicularis. Life sciences. 2013;92(3):187-92.
10- Ramadan, A.T., Abdel-Rahman, R.M., El-Behairy, M. A., Ismail, A.I, Mahmoud, M.M. The Thermodynamics of complexation of transition and lanthanides metal ions by 3- (α-carboxy -methylaminobenzylidene hydrazine)- 5,6-diphenyl-1,2,4-triazine. Thermochim. Acta , 1993:222 (2):291-303.
11- Atmaca, G. Antioxidant effects of sulfur-containing amino acids. Yonsei Med. J. 2004, 45, 776–788.
12- Rezanka T, Sobotka M, Spízek J, Sigler K. Pharmacologically active sulfur-containing compounds. Anti-Infective Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Infective Agents). 2006;5(2):187-224.
13- Sbirna, L.S., Muresan,V, Sbiren, S, Muresani, NComplex compounds of nickel (II) with bidentate heterocyclic ligands using both S and N as donor atoms. J. Indian Chem. Soc. 2005; 82; 389 – 392.
14- Choudhary, M.I., Abbas, G., Ali, S., Shuja, S., Khalid, N., Khan, K.M., Atta-ur-Rahman and Basha, F.Z.,. Substituted benzenediol Schiff bases as promising new anti-glycation agents. Journal of enzyme inhibition and medicinal chemistry, 2011;26(1); 98-103.
15- Lal Shyaula, S., Abbas, G., Siddiqui, H., A Sattar, S., Iqbal Choudhary, M. and Z Basha, F., Synthesis and antiglycation activity of kaempferol-3-O-rutinoside (Nicotiflorin). Medicinal Chemistry, 2012; 8(3);415-420.
16- Abid, O.U.R., Babar, T.M., Ali, F.I., Ahmed, S., Wadood, A., Rama, N.H., Uddin, R., Khan, A. and Choudhary, M.I.,. Identification of novel urease inhibitors by high-throughput virtual and in vitro screening. ACS medicinal chemistry letters, 2010; 1(4);145-149.
17- Matsuda H, Wang T, Managi H, Yoshikawa M. Structural requirements of flavonoids for inhibition of protein glycation and radical scavenging activities. Bioorganic & medicinal chemistry. 2003;11(24):5317-23.
18- Duraisamy Y, Gaffney J, Slevin M, Smith CA, Williamson K, Ahmed N. Aminosalicylic acid reduces the antiproliferative effect of hyperglycaemia, advanced glycation endproducts and glycated basic fibroblast growth factor in cultured bovine aortic endothelial cells: comparison with aminoguanidine. InVascular Biochemistry 2003:143-153.
19- Matsuura N, Aradate T, Sasaki C, Kojima H, Ohara M, Hasegawa J, Ubukata M. Screening System for the Maillard Reaction Inhibitor from Natural Product Extracts. Journal of health science. 2002;48(6):520-6.
20- Cervantes-Laurean D, Schramm DD, Jacobson EL, Halaweish I, Bruckner GG, Boissonneault GA. Inhibition of advanced glycation end product formation on collagen by rutin and its metabolites. The Journal of nutritional biochemistry. 2006;17(8):531-40.
21- Nagasawa T, Tabata N, Ito Y, Nishizawa N, Aiba Y, Kitts DD. Inhibition of glycation reaction in tissue protein incubations by water soluble rutin derivative. Biochemistry of Diabetes and Atherosclerosis 2003;3-10.
22- Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. Journal of immunological methods. 1983;65(1-2):55-63.
23- Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival: modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. Journal of immunological methods. 1986;89(2):271-7.
24- Nakagawa T, Yokozawa T, Terasawa K, Shu S, Juneja LR. Protective activity of green tea against free radical-and glucose-mediated protein damage. Journal of Agricultural and Food Chemistry. 2002;50(8):2418-22.
25- Lehman TD, Ortwerth BJ. Inhibitors of advanced glycation end product-associated protein cross-linking. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2001;1535(2):110-9.
26- J W Ludlow, J A Guikema, R A Consigli, Use of 5-(4-dimethylaminobenzylidene)rhodanine in quantitating silver grains eluted from autoradiograms of biological material.Analytical Biochemistry 1986-04-01 .
27- Halmi, N. S. Differentiation of two types of basophils in the adenohypophysis of the rat and the mouse. Stain Technology, 1952; 27(1); 61-64.
28- Bruno, P., Caselli, M., Traini, A., & Zuffianò, A. A contribution to the use of thorin as an analytical reagent: spectrophotometric study of its complexation with barium and application to sulphate determination in atmospheric particulates. Talanta, 1984; 31(7); 479-487.
29- Suoyan, B., Tongli, W., & Jinying, B. Catalytic Spectrophotometric Determination of Trace Nitrite Based on the Oxidation of Light Green SF by Potassium Bromate [J]. Chinese Journal of Analytieal Chemistry, 1995;2; 015.
30- S. Chen, I. Zhitomirsky, Polypyrrole electrodes doped with sulfanilic acid azochromotrop for electrochemical supercapacitors, Journal of Power Sources, 2013;243(1), 865–871
31- Tamás Pálfi, László Wojnárovits, Erzsébet Takács, Mechanism of azo dye degradation in Advanced Oxidation Processes: Degradation of Sulfanilic Acid Azochromotrop and its parent compounds in aqueous solution by ionizing radiation, Radiation Physics and Chemistry, 2011;80(3),462–470
32- Moutinho IL1, Bertges LC, Assis RV. Prolonged use of the food dye tartrazine (FD&C yellow no 5) and its effects on the gastric mucosa of Wistar rats. Braz J Biol. 2007 ;67(1):141-5.
33- Ugochukwu, C., Ihentuge, C. and Okechukwu, H.,. Evaluation of Toxicological Effects of Tartrazine Food Additive on histomorphic architecture of liver of Wistar Rats. The FASEB Journal, 2015;29(1),544-9.
34- Lohrmann, R. and Khorana, H.G. Studies on Polynucleotides. LII. 1 The Use of 2, 4, 6-Triisopropylbenzenesulfonyl Chloride for the Synthesis of Internucleotide Bonds2. Journal of the American Chemical Society, 1966;88(4),829-833.
35- Ghani, U., & Ullah, N. New potent inhibitors of tyrosinase: novel clues to binding of 1, 3, 4-thiadiazole-2 (3H)-thiones, 1, 3, 4-oxadiazole-2 (3H)-thiones, 4-amino-1, 2, 4-triazole-5 (4H)-thiones, and substituted hydrazides to the dicopper active site. Bioorganic & medicinal chemistry, 2010; 18(11), 4042-4048.
36- , Yoshimichi Tsuru, Tatsuya Kawada, Daijiro Terasaki, Takashi Kojima, Waichiro Idzutsu Liquid Redox Desulfurization Using 2-Nitroso-1-Naphthol-4-Sulfonic Acid as Redox Catalyst. Journal of the Fuel Society of Japan, 1981; 60 (1),58-64
37- Hisaindee, S., Al-Kaabi, L., Ajeb, S., Torky, Y., Iratni, R., Saleh, N.I. and AbuQamar, S.F. Antipathogenic effects of structurally-related Schiff base derivatives: Structure–activity relationship. Arabian Journal of Chemistry, 2015;8(6),828-836.
38- Kenar JA. Reaction chemistry of gossypol and its derivatives. Journal of the American Oil Chemists' Society. 2006;83(4):269-302.
39- Royer RE, Deck LM, Campos NM, Hunsaker LA, Vander Jagt DL. Biologically active derivatives of gossypol: synthesis and antimalarial activities of peri-acylated gossylic nitriles. Journal of medicinal chemistry. 1986;29(9):1799-801.
40- Baram NI, Ismailov AI. Biological activity of gossypol and its derivatives. Chemistry of Natural Compounds. 1993;29(3):275-87.
41- Tukfatullina II, Tilyabaev KZ, Mamadrakhimov A, Salakhutdinov BA, Kamaev FG, Yuldashev AM, Dowd MK, Talipov SA, Ibragimov BT, Aripov TF. Membrane-active properties and antiradical activity of gossypol and its derivatives. Chemistry of natural compounds. 2008;44(4):440-5.