Generic placeholder image

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry


ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

Research Article

In Silico and In Vitro Studies of the Inhibitory Effect of Antihistamine Drug Cyproheptadine Hydrochloride on Human Salivary Alpha Amylase

Author(s): Benguechoua Madjda*, Benarous Khedidja, Nia Samira and Yousfi Mohamed

Volume 20 , Issue 3 , 2021

Published on: 23 October, 2020

Page: [233 - 238] Pages: 6

DOI: 10.2174/1871523019666201023111825

Price: $65


Background: For the first time, the inhibitory effects on the human salivary alpha-amylase activity of the anti-inflammatory drugs indomethacin, diclofenac sodium, ketoprofen, diclofenac potassium, diclofenac, triamcinolone acetonide, and the antihistamine drugs levocetirizine dihydrochloride, desloratadine, cycloheptadine hydrochloride, have been investigated to confirm the other properties of these drugs.

Objective: This study aimed to determine the effect of nine known drugs on human salivary α-amylase in vitro and the nature of interactions with structure-activity relationship using molecular docking experiments.

Methods: The inhibition of human salivary alpha amylase by the six anti-inflammatory and three antihistamine drugs has been carried out using the new method that has been proved in our previous work. Molecular docking has been achieved for the first time for these drugs using the Auto- Dock Vina program.

Results: Cyproheptadine hydrochloride presented the highest inhibitory activity against α-amylase with IC50=0.7 mg/ml, while the other drugs showed weak activities (IC50 > 2 mg/ml).

Conclusion: We conclude that Cyproheptadine hydrochloride, which was studied by docking experiments, exhibited the best inhibitory activity on salivary α-amylase in vitro & in silico.

Keywords: Inhibition activity, human salivary α-amylase, anti-inflammatory drugs, antihistamine drugs, cyproheptadine hydrochloride, molecular docking.

Graphical Abstract
Rajagopalan, G.; Krishnan, C. Alpha-amylase production from catabolite derepressed Bacillus subtilis KCC103 utilizing sugarcane bagasse hydrolysate. Bioresour. Technol., 2008, 99(8), 3044-3050.
[] [PMID: 17644331]
Smith, M.; Morton, D. The Mouth Salivary Glands and Oesophagus In: The Digestive System; , 2010.
Nakajima, K.; Nemoto, T.; Muneyuki, T.; Kakei, M.; Fuchigami, H.; Munakata, H. Low serum amylase in association with metabolic syndrome and diabetes: A community-based study. Cardiovasc. Diabetol., 2011, 10, 34.
[] [PMID: 21496338]
Mandel, A.L.; Breslin, P.A. High endogenous salivary amylase activity is associated with improved glycemic homeostasis following starch ingestion in adults. J. Nutr., 2012, 142(5), 853-858.
[] [PMID: 22492122]
Haslam, D.W.; James, W.P. Obesity. Lancet, 2005, 366(9492), 1197-1209.
[] [PMID: 16198769]
Saiedullah, M. Insulin Sensitivity or Resistance in Type 2 Diabetes Mellitus with Obesity. Diabetes Case Rep., 2016, 1, e102.
Cakir, O.O.; Yildiz, M.; Kulaksizoglu, M. Visceral fat volume is a better predictor for insulin resistance than abdominal wall fat index in patients with prediabetes and type 2 diabetes mellitus. Intern. Med., 2016, 6, 220.
Lopes, D.N.; Wilson, C.T.A.; Ferreira de Mello, J.; Rodrigues, A.T. Multi insulin sensitization with tolerante to new therapeutic option: Degludec. J. Diabetes Metab., 2016, 7, 668.
Tabish, S.A. Is diabetes becoming the biggest epidemic of the twenty-first century? Int. J. Health Sci. (Qassim), 2007, 1(2), V-VIII.
[PMID: 21475425]
Kameya, A.; Hayakawa, T.; Noda, A.; Kondo, T. Differential determination of serum isoamylase using an amylase inhibitor and its clinical application. Am. J. Gastroenterol., 1985, 80(1), 54-59.
[PMID: 3966456]
Worning, H. Chronic pancreatitis: pathogenesis, natural history and conservative treatment. Clin. Gastroenterol., 1984, 13(3), 871-894.
[] [PMID: 6386243]
Yanai, K.; Rogala, B.; Chugh, K.; Paraskakis, E.; Pampura, A.N.; Boev, R. Safety considerations in the management of allergic diseases: focus on antihistamines. Curr. Med. Res. Opin., 2012, 28(4), 623-642.
[] [PMID: 22455874]
da Costa, B.R.; Reichenbach, S.; Keller, N.; Nartey, L.; Wandel, S.; Jüni, P.; Trelle, S. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet, 2017, 390(10090), e21-e33.
[] [PMID: 28699595]
Debnath, D. Biofuels, food security, and sustainability; Academic Press: Cambridge, Massachusetts, 2019.
Samira, N.I.A.; Khedidja, B.E.N.A.R.O.U.S.; Manel, L.A.K.A.A.S.; Israa, S.A.D.E.K.I.; Mohamed, Y.O.U.S.F.I. New inhibition detection method with molecular docking studies using some drugs on human salivary alpha amylase activity. Antiinflamm. Antiallergy Agents Med. Chem., 2020, 20(1), 10-19.
[] [PMID: 31899682]
Kim, S.; Thiessen, P.A.; Bolton, E.E.; Chen, J.; Fu, G.; Gindulyte, A.; Han, L.; He, J.; He, S.; Shoemaker, B.A.; Wang, J.; Yu, B.; Zhang, J.; Bryant, S.H. PubChem Substance and Compound databases. Nucleic Acids Res., 2016, 44(D1), D1202-D1213.
[] [PMID: 26400175]
Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The Protein Data Bank. Nucleic Acids Res., 2000, 28(1), 235-242.
[] [PMID: 10592235]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[] [PMID: 19399780]
BIOVIA, D.S. Discovery Studio Modeling Environment 2016.
Serseg, T.; Benarous, K. The Inhibitory Effect of Some Drugs on Candida rugosa Lipase and Human Pancreatic Lipase: In vitro and In silico Studies. Endocr. Metab. Immune Disord. Drug Targets, 2018, 18(6), 602-609.
[] [PMID: 29557755]
Khedidja, B.; Madjda, B.; Abderrahmane, G. Antiallergy drugs as potent inhibitors of lipase with structure-activity relationships and molecular docking. Antiinflamm. Antiallergy Agents Med. Chem., 2018, 17(2), 95-101.
[] [PMID: 30198443]
Samira, N.; Khedidja, B.; Fatima, Z.A.; Khadidja Nour, E.C.; Mohamed, Y. In silico and in vitro study of the inhibitory effect of some anti-inflammatory drugs on two lipases. Antiinflamm. Antiallergy Agents Med. Chem., 2019, 19(4), 387-392.
[] [PMID: 31518226]
Ramasubbu, N.; Paloth, V.; Luo, Y.; Brayer, G.D.; Levine, M.J. Structure of human salivary alpha-amylase at 1.6 A resolution: implications for its role in the oral cavity. Acta Crystallogr. D Biol. Crystallogr., 1996, 52(Pt 3), 435-446.
[] [PMID: 15299664]
Taha, M.; Irshad, M.; Imran, S.; Rahim, F.; Selvaraj, M.; Almandil, N.B.; Mosaddik, A.; Chigurupati, S.; Nawaz, F.; Ismail, N.; Ibrahim, M. Thiazole based carbohydrazide derivatives as α-amylase inhibitor and their molecular docking study. Heteroatom Chem., 2019, 8, 7502347.
Hung Jhong, C.; Riyaphan, J.; Hung Lin, S.; Hung Lin, S.; Chia, Y. Screening alpha-glucosidase and alpha-amylaseinhibitors from natural compounds by molecular docking in silico. Biofactors, 2015, 41(4), 1219.
Martinez-Gonzalez, A.I.; Díaz-Sánchez, Á.G.; de la Rosa, L.A.; Bustos-Jaimes, I.; Alvarez-Parrilla, E. Inhibition of α-amylase by flavonoids: Structure activity relationship (SAR). Spectrochim. Acta A Mol. Biomol. Spectrosc., 2019, 206, 437-447.
[] [PMID: 30172871]
Yilmazer-Musa, M.; Griffith, A.M.; Michels, A.J.; Schneider, E.; Frei, B. Inhibition of α-amylase and α-glucosidase activity by tea and grape seed extracts and their constituent catechins. J. Agric. Food Chem., 2012, 60(36), 8924-8929.
[] [PMID: 22697360]

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