Asian Journal of Pharmaceutical Research

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Design, In-Silico ADME Study And Molecular Docking Study of Novel Quinoline-4-on Derivatives as Factor Xa Inhibitor As Potential Anti-coagulating Agents


Affiliations
1 Research Scholar, Department of Pharmaceutical Chemistry, A.R College of Pharmacy and G.H Patel Institute of Pharmacy, Vallabh Vidhyanagar, Anand, Gujarat, India
2 Professor, Department of Pharmaceutical Chemistry, A.R College of Pharmacy and G.H Patel Institute of Pharmacy, Vallabh Vidhyanagar, Anand, Gujarat, India
     

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The main aim of present work is to identification of potency of novel quinoline-4-one derivatives as a factor Xa inhibitors by in-silico ADME study and molecular docking study. Factor Xa is enzyme which play major role in blood coagulation process by conversation of prothrombine to thrombine. Thrombine is the protein which converts fibrinogen to fibrin (clot). Inhbition of factor Xa is altimetly inhbition of blood coagulation process. Due to the abnormal blood coagulation, serious to very serious problems can create and will lead to death. Betrixaban, Rivaroxaban, Epixaban and Edoxaban which are FDA approval dugs as factor Xa inhibitors. They are very potent drugs and very few side effects compare to other available anti-coagulating drugs so they was taken as a reference molecules for current study. Some novel quinoline-4-one derivatives was design and screened for factor Xa enzyme. We design 26 compounds and first they screen for in-silico ADME parameters. Very few compounds not pass Lipinski rule. A majority compound shows excellent in-silico ADME properties. In molecular docking study almost all compound shows near binding energy to reference drug and shows almost near dock score. Q23 and Q26 show excellent inhibitory activity against Factor Xa. 13 molecules shows very near dock score compare to reference drugs. This study became a reference and provides valuable data for the synthesis, in-vitro and in-vivo evaluation of quinolone-4-on derivatives as Factor Xa inhibitors.


Keywords

Quinoline-4-on, Factor Xa, In-Silico ADME/T, Molecular Docking
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  • Delilah McCarty and April Robinson. Factor Xa inhibitors: a novel therapeutic class for the treatment of nonvalvular atrial fibrillation. Ther Adv Cardiovasc Dis. 2016; 10(1): 37–49. DOI: 10.1177/ 1753944715605011.

  • Alexander G.G. Turpie. Oral, Direct Factor Xa Inhibitors in Development for the Prevention and Treatment of Thromboembolic Diseases. Arteriosclerosis Thrombosis, and Vascular Biology. 2007; 27 :1238–1247. https://doi.org/10.1161/ATVBAHA.107.139402

  • Patel Nirav R. Patel Dushyant V. Murumkar Prashant R. Yadav. Mange Ram (2016). Contemporary developments in the discovery of selective factor Xa inhibitors: A review. European Journal of Medicinal Chemistry. 2016; S0223523416304378. doi:10.1016/j.ejmech.2016.05.039

  • Chan NC. Bhagirath V. Eikelboom JW. Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag, 2015; 11: 343–351. doi: 10.2147/VHRM.S63060

  • Baker D.E. Formulary Drug Review: Betrixaban. Hospital Pharmacy, 2018; 53(1): 29–37. doi.org/10.1177/0018578717724805

  • J. Beyer-Westendorf et al. Betrixaban for prevention of venous thromboembolism in acute medically ill patients. Eur Heart J., 2018; 20 (Supplement E): E16–E22. doi: 10.1093/eurheartj/suy017.

  • Nikunj Patadiya and Rajesh Dumpala; “A High-Profile Review On New Oral Clotting Factor Xa Inhibitor: Betrixaban” European Journal Of Pharmaceutical And Medical Research. 2021; 8(1): 239-247.

  • Turpie AG, Bauer KA, Davidson BL, et al. A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT). Thromb Haemost, 2009; 101(1): 68–76. doi: 10.1016/s0140- 6736(88)92070-3

  • Stuart J. Connolly et al. Betrixaban compared with warfarin in patients with atrial fibrillation: results of a phase 2, randomized, dose-ranging study (ExploreXa). Eur Heart J., 2013; 34, 1498– 1505. doi: 10.1093/eurheartj/eht039

  • H. Guy et al. Cost-Effectiveness of Betrixaban Compared with Enoxaparin for Venous Thromboembolism Prophylaxis in Nonsurgical Patients with Acute Medical Illness in the United States. PharmacoEconomics, 2019; 37: 701–714. 8. Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med, 2016; 375(6): 534–544. doi: 10.1007/s40273-018- 0757-8.

  • Ferreira L, Santos R, Oliva G and Andricopulo A. Molecular Docking and Structure-Based Drug Design Strategies. Molecules; 2015, 20: 13387. doi: 10.3390/molecules200713384.

  • Chaudhary Kk. Mishra N. A Review on Molecular Docking: Novel Tool for Drug Discovery. JSM Chem. 2016; 4(3): 1029. doi: 10.4172/2155-3872.1000356.

  • Manish Devgan. Homology modeling and molecular docking studies of DNA replication licensing factor minichromosome maintenance protein 5 (MCM5). Asian J. Pharm. Tech. 2015; 5(1): 17-22. doi: 10.5958/2231-5713.2015.00004.5.

  • Sindhu. T. J, Arathi. K. N, Akhilesh K. J, Anju. Jose, Binsiya K. P, Blessy Thomas, Elizabeth Wilson. Antiviral screening of Clerodol derivatives as COV 2 main protease inhibitor in Novel Corona Virus Disease: In silico approaches. Asian J. Pharm. Tech. 2020; 10(2): 60-64. doi:10.5958/2231-5713.2020.00012.4

  • M. Sravani, N. Duganath, Deepak Reddy Gade, Sandeep Reddy C. H. Insilico Analysis and Docking of Imatinib Derivatives Targeting BCR-ABL Oncoprotien for Chormic Myeloid Leukemia. Asian J. Research Chem. 2012; 5(1): 153-158

  • Tanveer Hasan, Raza Murad Ghalib, Sayed Hasan Mehdi, P.K Singh, S.S.R. Bagri. Normal Mode Analysis, Electronic Parameters and molecular docking study of 3,5,4’-Trihydroxy-6,7- Dimethoxy-Flavone (Eupalitin) using first Principle. Asina J. Research Chem. 2017; 10(6): 789-797. doi:10.5958/0974- 4150.2017.00132.8

  • Samir Zeroual, Ismmail Daoud, Randa Gaouaoui, Said Ghalem. In Vitro and Molecular Docking Studies of DPPH woth Phoenix dactylifera L. (Deglet-Nour) Crude Fruits extract and Evaluation of their Antioxidant Activity. Asian J. Research Chem. 2020; 13(1): 52-59. doi:10.5958/0974-4150.2020.00012.7

  • Sindhu. T. J, Akhilesh K. J, Anju. Jose, Binsiya K. P, Blessy Thomas, Elizabeth Wilson. Antibacterail Screening of Clerodendrum infortunatum leaves: Experimental and Molecular docking studies. doi:10.5958/0974-4150.2020.00026.7

  • Sudhakar P, Poorana Pushkalai S, Sabarinath C, Priyadharshini S, Haripriya S. Molecular docking and synthesis of 1,2,4 – triazin analogue of diclofenac as potential ligand for parkinson’s. Res. J. Pharamcology and Pharmacodynamics. 2018; 10(1): 08-12. doi:10.5958/2321-5836.2018.00002.2

  • Jeyabaskar Suganya, Mahendran Radha, Sharanya Manoharan, Vinoba. V, Astral Francis. Virtual Screening and Analysis of Bioactive Compounds of Momoradica charantia against Diabetess using Computational Approches. Research J. Pharm. and Tech. 2017; 10(10): 3353-3360. doi: 10.5958/0974-360X.2017.00596.0

  • Pavlo V. Zadorozhnii, Vadym V. Kiselev, NAtaliia O. Teslenko, Aleksandr V. Kharchenko, Ihor O. Pokotylo, Oxana v. Okhtina, Oxana V. Kryshchyk. In Silico Prediction and Molecular Dockling Studies of N-Amidoalkylated Derivatives of 1,3,4-Oxadiazole as COX-1 and COX-2 Inhibitors. Research J. Pharm. and Tech. 2007; 10(11): 3957-3963. doi: 10.5958/0974-360X.2017.00718.1

  • Himadri Shekhaar Baul, Muniyan Rajiniraja. Favorable binding of Quercetin to α-Synuclein as potential target in Parkinson disease: An Insilico approach. Research J. Pharm. and Tech. 2018; 11(1): 203-206. doi: 10.5958/0974-360X.2018.00038.0


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  • Design, In-Silico ADME Study And Molecular Docking Study of Novel Quinoline-4-on Derivatives as Factor Xa Inhibitor As Potential Anti-coagulating Agents

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Authors

Nikunj Patadiya
Research Scholar, Department of Pharmaceutical Chemistry, A.R College of Pharmacy and G.H Patel Institute of Pharmacy, Vallabh Vidhyanagar, Anand, Gujarat, India
Vipul Vaghela
Professor, Department of Pharmaceutical Chemistry, A.R College of Pharmacy and G.H Patel Institute of Pharmacy, Vallabh Vidhyanagar, Anand, Gujarat, India

Abstract


The main aim of present work is to identification of potency of novel quinoline-4-one derivatives as a factor Xa inhibitors by in-silico ADME study and molecular docking study. Factor Xa is enzyme which play major role in blood coagulation process by conversation of prothrombine to thrombine. Thrombine is the protein which converts fibrinogen to fibrin (clot). Inhbition of factor Xa is altimetly inhbition of blood coagulation process. Due to the abnormal blood coagulation, serious to very serious problems can create and will lead to death. Betrixaban, Rivaroxaban, Epixaban and Edoxaban which are FDA approval dugs as factor Xa inhibitors. They are very potent drugs and very few side effects compare to other available anti-coagulating drugs so they was taken as a reference molecules for current study. Some novel quinoline-4-one derivatives was design and screened for factor Xa enzyme. We design 26 compounds and first they screen for in-silico ADME parameters. Very few compounds not pass Lipinski rule. A majority compound shows excellent in-silico ADME properties. In molecular docking study almost all compound shows near binding energy to reference drug and shows almost near dock score. Q23 and Q26 show excellent inhibitory activity against Factor Xa. 13 molecules shows very near dock score compare to reference drugs. This study became a reference and provides valuable data for the synthesis, in-vitro and in-vivo evaluation of quinolone-4-on derivatives as Factor Xa inhibitors.


Keywords


Quinoline-4-on, Factor Xa, In-Silico ADME/T, Molecular Docking

References