Generic placeholder image

Letters in Drug Design & Discovery


ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Research Article

Antiglycation Activity of N, N-Diethylthiobarbiturates Derivatives

Author(s): Momin Khan*, Ghulam Ahad, Ajmal Khan, Sana Shah, Kanwal, Uzma Salar, Syed Muhammad Salman and Khalid Mohammed Khan*

Volume 17 , Issue 4 , 2020

Page: [411 - 417] Pages: 7

DOI: 10.2174/1570180816666190516111516

Price: $65


Background: Previous identification of N,N-diethylthiobarbiturates as potential α-glucosidase inhibitory potential prompted us to investigate the antiglycation activity of these synthetic compounds (1-25) in order to identify the lead candidates for their possible antidiabetic potential.

Methods: Synthetic compounds (1-25) were evaluated for their antiglycation activity using Bovine Serum Albumin assay (BSA).

Result: Compounds exhibited varying degree of inhibition in the range of IC50 = 61.16 ± 2.3 - 656.71 ± 2.5 µM as compared to the standard rutin (IC50 = 294.5 ± 1.50 µM). Among the twenty five synthetic molecules, seven compounds showed good activity in comparison with the standard. Compound 4 (IC50 = 61.16 ± 2.3 µM) having hydroxy substituents was the most active molecule of the library. This study revealed that compound 4 has dual acting antidibetic molecule.

Conclusion: In conclusion, the synthetic N,N-diethylthiobarbiturates can act as lead molecules. Furthermore, synthetic variations on N,N-diethylthiobarbituric acid moiety might be helpful in generating a library of potential anti diabetic agent. Especially, compound 4 has been identified as dual acting antidiabetic agent i.e. α-glucosidase inhibitor and antiglycating agent.

Keywords: N, N-Diethylthiobarbiturates, antiglycation, aromatic aldehydes, dual inhibitor, rutin, α-glucosidase inhibitor.

Graphical Abstract
Guillén Sans, R.; Guzmán Chozas, M. Historical aspects and applications of barbituric acid derivatives. A review. Pharmazie, 1988, 43(12), 827-829.
[PMID: 3073393]
Cutting, W.C. Book of Pharmacol, 3rd ed; Meredith Publishing: New York, 1967.
Vijaya Laxmi, S.; Thirupathi Reddy, Y.; Suresh Kuarm, B.; Narsimha Reddy, P.; Crooks, P.A.; Rajitha, B. Synthesis and evaluation of chromenyl barbiturates and thiobarbiturates as potential antitubercular agents. Bioorg. Med. Chem. Lett., 2011, 21(14), 4329-4331.
[] [PMID: 21684158]
Dabholkar, V.V.; Tripathi, D.R. Synthesis of Biginelli products of thiobarbituric acids and their antimicrobial activity. J. Serb. Chem. Soc., 2010, 75, 1033.
Kidwai, M.; Thakur, R.; Mohan, R. Ecofriendly synthesis of novel antifungal (thio)barbituric acid derivatives. Acta Chim. Slov., 2005, 52, 88.
Lee, J.H.; Lee, S.; Park, M.Y.; Myung, H. Characterization of thiobarbituric acid derivatives as inhibitors of hepatitis C virus NS5B polymerase. Virol. J., 2011, 8, 18.
[] [PMID: 21235805]
Balas, V.I.; Verginadis, I.I.; Geromichalos, G.D.; Kourkoumelis, N.; Male, L.; Hursthouse, M.B.; Repana, K.H.; Yiannaki, E.; Charalabopoulos, K.; Bakas, T.; Hadjikakou, S.K. Synthesis, structural characterization and biological studies of the triphenyltin(IV) complex with 2-thiobarbituric acid. Eur. J. Med. Chem., 2011, 46(7), 2835-2844.
[] [PMID: 21521629]
Wiggins, L.F.; James, J.W.; Gittos, M.W. US Patent 3, 930, 006 (1975) Chem. Abstr, 1976, 84140749k .
Zawisza, T.; Matczak, H.; Kowalczyk-Bronisz, S.H.; Jakobiec, T. A versatile approach for the synthesis of thiobarbiturate analogues. Pol. Arch. Immunol. Ther. Exp., 1981, 29, 235.
Izatt, R.M.; Christensen, J.J.; Rytting, J.H. Sites and thermodynamic quantities associated with proton and metal ion interaction with ribonucleic acid, deoxyribonucleic acid, and their constituent bases, nucleosides, and nucleotides. Chem. Rev., 1971, 71(5), 439-481.
[] [PMID: 5126179]
Cutting, W.C. Hand Book of Pharmacology, 3rd ed; Appleton-Century-Crofts, Meredith Publishing Company: New York, 1967.
Kazyak, L.; Knoblock, E.C. Application of gas chromatography to analytical toxicology. Anal. Chem., 1968, 35, 1448.
Parker, K.D.; Fontan, C.R.; Kirk, P.L. Rapid gas chromatographic method for screening of toxicological extracts for alkaloids, barbiturates, sympathomimetic amines, and tranquilizers. Anal. Chem., 1963, 35, 356.
Abou-Eittah, R.; Osman, A. Studies on the formation of mixed-ligand complexes of cobalt(II) with ammonia and some barbiturates. J. Inorg. Nucl. Chem., 1979, 41, 1079.
Eichorn, G.L. Inorganic Biochemistry; Vol. 2 Elsevier: NewYork, N.Y., 1973. (Chapters 32 and 33).
Bassani, D.M. From supramolecular photochemistry to self-assembled photoactive architectures: The emergence of photochemical nanosciences. Chimia (Aarau), 2006, 60, 175.
Ikeda, A.; Tanaka, Y.; Nobusawa, K.; Kikuchi, J. Solubilization of single-walled carbon nanotubes by supramolecular complexes of barbituric acid and triaminopyrimidines. Langmuir, 2007, 23(22), 10913-10915.
[] [PMID: 17894514]
Ahmed, N. Advanced glycation endproducts--role in pathology of diabetic complications. Diabetes Res. Clin. Pract., 2005, 67(1), 3-21.
[] [PMID: 15620429]
Brownlee, M. Lilly Lecture 1993. Glycation and diabetic complications. Diabetes, 1994, 43(6), 836-841.
[] [PMID: 8194672]
Khalifah, R.G.; Baynes, J.W.; Hudson, B.G. Amadorins: Novel post-amadori inhibitors of advanced glycation reactions. Biochem. Biophys. Res. Commun., 1999, 257(2), 251-258.
[] [PMID: 10198198]
Vigorita, M.G.; Ottanà, R.; Maccari, R.; Monforte, F.; Bisignano, G.; Pizzimenti, F.C. Synthesis and in vitro antimicrobial and antitumoral screening of novel lipophilic isoniazid analogues. VI. Boll. Chim. Farm., 1998, 137(7), 267-276.
[PMID: 9795482]
Marles, R.J.; Farnsworth, N.R. Antidiabetic plants and their active constituents. Phytomedicine, 1995, 2(2), 137-189.
[] [PMID: 23196156]
Hunt, J.V.; Bottoms, M.A.; Mitchinson, M.J. Oxidative alterations in the experimental glycation model of Diabetes Mellitus are due to protein-glucose adduct oxidation. Some fundamental differences in proposed mechanisms of glucose oxidation and oxidant production. Biochem. J., 1993, 291(Pt 2), 529-535.
[] [PMID: 8484733]
Ahmad, M.S.; Ahmed, N. Antiglycation properties of aged garlic extract: Possible role in prevention of diabetic complications. J. Nutr., 2006, 136(3)(Suppl.), 796S-799S.
[] [PMID: 16484566]
Yang, J.; Guo, J.; Yuan, J. In vitro antioxidant properties of rutin. LWT, 2008, 41, 1060.
Dubey, S.; Ganeshpurkar, A.; Ganeshpurkar, A.; Bansal, D.; Dubey, N. Glycolytic enzyme inhibitory and antiglycation potential of rutin. Fut. J. Pharma. Sci., 2017, 3, 158.
(a)Monnier, V.M. Intervention against the Maillard reaction in vivo. Arch. Biochem. Biophys., 2003, 419(1), 1-15.
[] [PMID: 14568003]
(b)Salar, U. Khan; K. M, Chigurupati; S., Taha; Wadood, A.; Vijayabalan, M.; Ghufran, V.M.; Perveen, S. New hybrid hydrazinyl thiazole substituted chromones: As potential α-amylase inhibitors and radical (DPPH &ABTS) scavengers. Sci. Rep., 2017, 5(1), 16980.
[] [PMID: 29209017]
(c)Adegboye, U.A.A.; Khan, K.M.; Salar, U.; Aboaba, S.A. Kanwal, Chigurupati S.; Fatima, I.; Taha, M.; Wadood, A.; Mohammad, J. I.; Khan, H.; Perveen, S. 2-Aryl benzimidazoles: Synthesis, in vitro α-amylase inhibitory activity, and molecular docking study. Eur. J. Med. Chem., 2018, 150, 248-260.
[] [PMID: 29533872]
(d)Taha, M.; Tariq Javid, M.; Imran, S.; Selvaraj, M.; Chigurupati, S.; Ullah, H.; Rahim, F.; Khan, F.; Islam Mohammad, J.; Mohammed Khan, K. Synthesis and study of the α-amylase inhibitory potential of thiadiazole quinoline derivatives. Bioorg. Chem., 2017, 74, 179-186.
[] [PMID: 28826047]
Khan, K.M.; Rahim, F.; Ambreen, N.; Taha, M.; Khan, M.; Jahan, H.; Najeebullah, S. A.; Iqbal, S.; Perveen S.; Choudhary, M. I. Synthesis of benzophenonehydrazone Schiff bases. Med. Chem., 2013, 9, 588.
[PMID: 23151265]
Rahbar, S. The discovery of glycated hemoglobin: A major event in the study of nonenzymatic chemistry in biological systems. Ann. N. Y. Acad. Sci., 2005, 1043, 9-19.
[] [PMID: 16037217]
Khan, M.; Khan, S.; Mulk, A.U.; Rahman, A.U.; Wadood, A.; Shams, S.; Ashraf, M.; Rahman, J.; Hameed, A.; Hussain, Z.; Khan, A.; Zaman, K.; Khan, K.M.; Perveen, S. Synthesis, molecular modeling and biological evaluation of 5-arylidene-N,N-diethylthiobarbiturates as potential α-glucosidase inhibitors. Med. Chem., 2019, 15(2), 175-185.
[] [PMID: 30207240]
Yeh, W.J.; Hsia, S.M.; Lee, W.H.; Wu, C.H. Polyphenols with antiglycation activity and mechanisms of action: A review of recent findings. J. Food Drug Anal., 2017, 25(1), 84-92.
[] [PMID: 28911546]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy