New Hybrid Scaffolds based on Hydrazinyl Thiazole Substituted Coumarin; As Novel Leads of Dual Potential; In Vitro α-Amylase Inhibitory and Antioxidant (DPPH and ABTS Radical Scavenging) Activities

Author(s): Uzma Salar, Khalid M. Khan*, Sridevi Chigurupati, Shazia Syed, Shantini Vijayabalan, Abdul Wadood, Muhammad Riaz, Mehreen Ghufran, Shahnaz Perveen.

Journal Name: Medicinal Chemistry

Volume 15 , Issue 1 , 2019

Submit Manuscript
Submit Proposal

Graphical Abstract:


Abstract:

Background: Despite many side effects associated, there are many drugs which are being clinically used for the treatment of type-II diabetes mellitus (DM). In this scenario, there is still need to develop new therapeutic agents with more efficacy and less side effects. By keeping in mind the diverse spectrum of biological potential associated with coumarin and thiazole, a hybrid class based on these two heterocycles was synthesized.

Method: Hydrazinyl thiazole substituted coumarins 4-20 were synthesized via two step reaction. First step was the acid catalyzed reaction of 3-formyl/acetyl coumarin derivatives with thiosemicarbazide to form thiosemicarbazone intermediates 1-3, followed by the reaction with different phenacyl bromides to afford products 4-20. All the synthetic analogs 4-20 were characterized by different spectroscopic techniques such as EI-MS, HREI-MS, 1H-NMR and 13C-NMR. Stereochemical assignment of the iminic double bond was carried out by the NOESY experiments. Elemental analysis was found in agreement with the calculated values.

Results: Compounds 4-20 were screened for α-amylase inhibitory activity and showed good activity in the range of IC50 = 1.829 ± 0.102-3.37 ± 0.17 µM as compared to standard acarbose (IC50 = 1.819 ± 0.19 µM). Compounds were also investigated for their DPPH and ABTS radical scavenging activities and displayed good radical scavenging potential. In addition to that molecular modelling study was conducted on all compounds to investigate the interaction details of compounds 4- 20 (ligands) with active site (receptor) of enzyme.

Conclusion: The newly identified hybrid class may serve as potential lead candidates for the management of diabetes mellitus.

Keywords: Coumarin, hydrazinyl thiazole, in vitro, in silico, α-amylase activity, DPPH, ABTS.

[1]
Sales, P.M.; Souza, P.M.; Simeoni, L.A.; Magalhães, P.O.; Silveira, D. α-Amylase inhibitors: a review of raw material and isolated compounds from plant source. J. Pharm. Pharmaceut. Sci., 2012, 15, 141-183.
[2]
Funke, I.; Melzig, M.F. Traditionally used plants in diabetes therapy: phytotherapeutics as inhibitors of alpha-amylase activity. Rev. Bras. Farmacogn., 2006, 16, 1-5.
[3]
Inzucchi, S.E. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA, 2002, 287, 360-372.
[4]
Göke, B.; Herrmann-Rinke, C. The evolving role of α‐glucosidase inhibitors. Diabetes Metabolism . Rev., 1998, 14, S31-S38.
[5]
He, L. Alpha-glucosidase inhibitors as agents in the treatment of diabetes. Diabetes Rev., 1998, 6, 132-145.
[6]
Whitcomb, D.C.; Lowe, M.E. Human pancreatic digestive enzymes. Dig. Dis. Sci., 2007, 52, 1-17.
[7]
Kandra, L. α-Amylases of medical and industrial importance. J. Mol. Struct. Theochem, 2003, 666, 487-498.
[8]
Van de Laar, F.A.; Lucassen, P.L.; Akkermans, R.P.; Van de Lisdonk, E.H.; Rutten, G.E.; Van Weel, C. Alpha-glucosidase inhibitors for type 2 diabetes mellitus (Cochrane Review). The Cochrane Library., 2005.
[9]
Cheng, A.Y.; Fantus, I.G. Oral antihyperglycemic therapy for type 2 diabetes mellitus. Canadian . Med. Assoc. J., 2005, 172, 213-226.
[10]
Tarling, C.A.; Woods, K.; Zhang, R.; Brastianos, H.C.; Brayer, G.D.; Andersen, R.J.; Withers, S.G. The search for novel human pancreatic α-amylase inhibitors: high-throughput screening of terrestrial and marine natural product extracts. ChemBioChem, 2008, 9, 433-438.
[11]
Hoult, J.; Paya, M. Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. Gen. Pharmacol.: Vascul. Syst., 1996, 27, 713-722.
[12]
Sashidhara, K.V.; Kumar, A.; Kumar, M.; Sarkar, J.; Sinha, S. Synthesis and in vitro evaluation of novel coumarin-chalcone hybrids as potential anticancer agents. Bioorg. Med. Chem. Lett., 2010, 20, 7205-7211.
[13]
Kidane, A.G.; Salacinski, H.; Tiwari, A.; Bruckdorfer, K.R.; Seifalian, A.M. Anticoagulant and antiplatelet agents: their clinical and device application (s) together with usages to engineer surfaces. Biomacromolecules, 2004, 5, 798-813.
[14]
Ma, T.; Liu, L.; Xue, H.; Li, L.; Han, C.; Wang, L.; Chen, Z.; Liu, G. Chemical library and structure-activity relationships of 11-demethyl-12-oxo calanolide A analogues as anti-HIV-1 agents. J. Med. Chem., 2008, 51, 1432-1446.
[15]
Kontogiorgis, C.A.; Hadjipavlou-Litina, D.J. Synthesis and biological evaluation of novel coumarin derivatives with a 7-azomethine linkage. Bioorg. Med. Chem. Lett., 2004, 14, 611-614.
[16]
Khan, K.M.; Saify, Z.S.; Khan, M.Z. Zia-Ullah; Iqbal, A.; Choudhary, M.I.; Atta-ur-Rahman; Perveen, S.; Chohan, Z.H.; Supuran, C.T. Synthesis of coumarin derivatives with cytotoxic, antibacterial and antifungal activity. J. Enzyme Inhib. Med. Chem., 2004, 19, 373-379.
[17]
Salar, U.; Khan, K.M.; Jabeen, A.; Faheem, A.; Fakhri, M.I.; Saad, S.M.; Perveen, S.; Taha, M.; Hammed, A. Coumarin sulfonates: As potential leads for ROS inhibition. Bioorg. Chem., 2016, 69, 34-47.
[18]
Kempen, I.; Papapostolou, D.; Thierry, N.; Pochet, L.; Counerotte, S.; Masereel, B.; Foidart, J-M.; Reboud-Ravaux, M.; Noël, A.; Pirotte, B. 3-Bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzo-pyran-3-carboxylate inhibits cancer cell invasion in vitro and tumour growth in vivo. British . J. Cancer, 2003, 88, 1111-1118.
[19]
Sashidhara, K.V.; Rosaiah, J.N.; Kumar, A.; Bhatia, G.; Khanna, A. Synthesis of novel benzocoumarin derivatives as lipid lowering agents. Bioorg. Med. Chem. Lett., 2010, 20, 3065-3069.
[20]
Kostova, I. Synthetic and natural coumarins as cytotoxic agents. Curr. Med. Chem. Anticancer Agents, 2005, 5, 29-46.
[21]
Musa, M.A.; Cooperwood, J.S.; Khan, M.O.F. A review of coumarin derivatives in pharmacotherapy of breast cancer. Curr. Med. Chem., 2008, 15, 2664-2679.
[22]
Peng, X-M.; L.V., Damu G.; Zhou, H. Current developments of coumarin compounds in medicinal chemistry. Curr. Pharm. Des., 2013, 19, 3884-3930.
[23]
Medina, F.G.; Marrero, J.G.; Macías-Alonso, M.; González, M.C.; Córdova-Guerrero, I.; García, A.G.T.; Osegueda-Robles, S. Coumarin heterocyclic derivatives: Chemical synthesis and biological activity. Nat. Prod. Rep., 2015, 32, 1472-1507.
[24]
Kashyap, S.J.; Garg, V.K.; Sharma, P.K.; Kumar, N.; Dudhe, R.; Gupta, J.K. Thiazoles: having diverse biological activities. Med. Chem. Res., 2012, 21, 2123-2132.
[25]
Siddiqui, N.; Arshad, M.F.; Ahsan, W.; Alam, M.S. Thiazoles: a valuable insight into the recent advances and biological activities. Int. J. Pharm. Sci. Drug Res., 2009, 1, 136-143.
[26]
(a)Arshad, T.; Khan, K.M.; Rasool, N.; Salar, U.; Hussain, S.; Asghar, H.; Ashraf, M.; Wadood, A.; Riaz, M.; Perveen, S.; Taha, M.; Ismail, N.H. 5-Bromo-2-aryl benzimidazole derivatives as non-cytotoxic potential dual inhibitors of α-glucosidase and urease enzymes. Bioorg. Chem., 2017, 72, 21-31.
(b)Khan, K.M.; Qurban, S.; Salar, U.; Taha, M.; Hussain, S.; Perveen, S.; Hameed, A.; Ismail, N.H.; Riaz, M.; Wadood, A. Synthesis, in vitro α-glucosidase inhibitory activity and molecular docking studies of new thiazole derivatives. Bioorg. Chem., 2016, 68, 245-258.
(c)Arshad, T.; Khan, K.M.; Rasool, N.; Salar, U.; Hussain, S.; Tahir, T.; Ashraf, M.; Wadood, A.; Riaz, M.; Perveen, S.; Taha, M.; Ismail, N.H. Syntheses, in vitro evaluation and molecular docking studies of 5-bromo-2-aryl benzimidazoles as α-glucosidase inhibitors. Med. Chem. Res., 2016, 25, 2058-2069.
(d)Javaid, K.; Saad, S.M.; Rasheed, S.; Moin, S.T.; Syed, N.; Fatima, I.; Salar, U.; Khan, K.M.; Perveen, S.; Choudhary, M.I. 2-Arylquinazolin-4(3H)-ones: A new class of α-glucosidase inhibitors. Bioorg. Med. Chem., 2015, 23, 7417-7421.
(e)Bano, B.; Abbasi, S.; Khan, J.A.J.; Hussain, S.; Rasheed, S.; Perveen, S.; Khan, K.M.; Choudhary, M.I. Antiglycation activity of quinoline derivatives- A new therapeutic class for the management of type 2 diabetes complications. Med. Chem., 2015, 11, 60-68.
(f)Abbasi, S.; Mirza, S.; Rasheed, S.; Hussain, S.; Khan, J.A.J.; Khan, K.M.; Perveen, S.; Choudhary, M.I. Benzothiazole derivatives: Novel inhibitors of methylglyoxal mediated glycation of protein in vitro. Med. Chem., 2014, 10, 824-835.
(g)Khan, K.M.; Khan, M.; Ambreen, N.; Taha, M.; Rahim, F.; Rasheed, S.; Saied, S.; Safi, H.; Perveen, S.; Choudhary, M.I. Oxindole derivatives: Synthesis and antiglycation activity. Med. Chem., 2013, 9, 681-688.
[27]
Salar, U.; Taha, M.; Khan, K.M.; Ismail, N.H.; Imran, S.; Perveen, S.; Gul, S.; Wadood, A. Syntheses of new 3-thiazolyl coumarin derivatives, in vitro α-glucosidase inhibitory activity, and molecular modeling studies. Eur. J. Med. Chem., 2016, 122, 196-204.
[28]
Asmat, U.; Abad, K.; Ismail, K. Diabetes mellitus and oxidative stress—a concise review. SPJ, 2016, 24, 547-553.
[29]
Kwon, Y-I.; Apostolidis, E.; Shetty, K. In vitro studies of eggplant (Solanum melongena) phenolics as inhibitors of key enzymes relevant for type 2 diabetes and hypertension. Bioresour. Technol., 2008, 99, 2981-2988.
[30]
Loh, S.P.; Hadira, O. In vitro inhibitory potential of selected Malaysian plants against key enzymes involved in hyperglycemia and hypertension. Malays. J. Nutr., 2011, 17, 77-86.
[31]
Tayyaba, N.; Muhammad, T.; Syahrul, I.; Sridevi, C.H.; Rahim, F.; Selvaraj, M.; Irshad, M. Synthesis of alpha amylase inhibitors based on privileged indole scaffold. Bioorg. Chem., 2017, 72, 248-255.
[32]
Suthakaran, R.; Somasekhar, G.; Sridevi, C.; Marikannan, M.; Suganthi, K.; Nagarajan, G. Synthesis, antiinflammatory, antioxi-dant and antibacterial activities of 7-methoxy benzofuran pyra-zoline derivatives. Asian J. Chem., 2007, 19, 3353-3362.
[33]
Sridevi, C.H.; Balaji, K.; Naidu, A.; Sudhakaran, R. Antioxidant, anti-inflammatory and histaminic activities of some phenyl pyrazolo benzothiazolo quinoxaline derivatives. Int. J. Chem. Sci., 2009, 7, 1117-1126.
[34]
Chigurupati, S.; Selvaraj, M.; Mani, V.; Selvarajan, K.K.; Mohammad, J.I.; Kaveti, B.; Bera, H.; Palanimuthu, V.R.; Teh, L.K.; Salleh, M.Z. Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies. Bioorg. Chem., 2016, 67, 9-17.
[35]
Leach, A.R.; Shoichet, B.K.; Peishoff, C.E. Prediction of protein-ligand interactions. Docking and scoring: Successes and gaps. J. Med. Chem., 2006, 49, 5851-5855.


Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 15
ISSUE: 1
Year: 2019
Page: [87 - 101]
Pages: 15
DOI: 10.2174/1573406414666180903162243
Price: $58

Article Metrics

PDF: 24
HTML: 2