Computational studies of some biscoumarin and biscoumarin thiourea derivatives as alfa-glucosidase inhibitors

Muhammad Tukur Ibrahim; Adamu Uzairu; Gideon Adamu Shallangwa; Abdulkadir Ibrahim

doi:10.18540/jcecvl4iss2pp0276-0285

Autores

Muhammad Tukur Ibrahim Ahmadu Bello University, Zaria
Adamu Uzairu Ahmadu Bello University, Zaria
Gideon Adamu Shallangwa Ahmadu Bello University, Zaria
Abdulkadir Ibrahim Ahmadu Bello University, Zaria

DOI:

https://doi.org/10.18540/jcecvl4iss2pp0276-0285

Palavras-chave:

⍺-glucosidase, QSAR, Molecular docking, Biscoumarin

Resumo

Quantitative structure-activity relationship and molecular docking studies of 35 compounds of Biscoumarins and Biscoumarins thiourea derivatives as alfa-glucosidase inhibitors was performed. Density Functional Theory (DFT) method was employed for complete geometry optimization of the alfa-glucosidase inhibitors. Genetic Function Algorithm (GFA) of the material studio was utilized to develop four models. Model 1 was found to be the best model with R² = 0.914362, R² _adj = 0.892953, Q2cv = 0.858197 and R² _pred = 0.614745. The proposed model is robustness and predicted with good internal and external validation. The descriptors should be considered when improving the inhibitory activities of biscoumarin derivatives against alfa-glucosidase. The docking results showed that ligands having Ortho substituted phenyl ring have good interactions with active site residues and good inhibitory activities as compared to ligands having either Para or Meta substituted phenyl ring except ligand 16 which has the highest docking scores of -12.5 kcal/mol but undergoes para substitution on the phenyl ring and formed hydrogen bond, hydrophobic and electrostatic interactions with the active residues of the enzyme. The QSAR model and molecular docking results agree with each other and give way to the designing of new inhibitors with better activity against alfa-glucosidase.

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Referências

ABDULFATAI, U.; UZAIRU, A.; & UBA, S. In Silico Study Of Some Anticonvulsant Compounds. Scholars’ Press Isbn: 978-3-330-65212-5, 2016.
ABDULFATAI, U.; UZAIRU, A.; & UBA, S. Quantitative Structure-Activity Relationship And Molecular Docking Studies Of A Series Of Quinazolinonyl Analogues As Inhibitors Of Gamma Amino Butyric Acid Aminotransferase. Journal Of Advanced Research, 8, 33-43, 2017.
ADENIJI, S. E.; UBA, S.; & UZAIRU, A. Quantitative Structure-Activity Relationship And Molecular Docking Of 4-Alkoxy-Cinnamic Analogues As Anti-Mycobacterium Tuberculosis. Journal Of King Saud University-Science, 2018.
AMIT, C.; PAYAL, C.; & R.K, D. Qsar Study Of 2,4-Dioxothiazolidine Antidiabetic Compounds, 2014.
ARTHUR, D. E.; UZAIRU, A.; MAMZA, P.; ABECHI, S. E.; & SHALLANGWA, G. Insilco Study On The Toxicity Of Anti-Cancer Compounds Tested Against Molt-4 And P388 Cell Lines Using Ga-Mlr Technique. Beni-Suef University Journal Of Basic And Applied Sciences, 5, 320-333, 2016.
AZIZ, M. T. A.; EL-ASMAR, M. F.; REZQ, A. M.; MAHFOUZ, S. M.; WASSEF, M. A.; FOUAD, H. H.; AHMED, H. H.; & TAHA, F. M. The Effect Of A Novel Curcumin Derivative On Pancreatic Islet Regeneration In Experimental Type-1 Diabetes In Rats (Long-Term Study). Diabetology & Metabolic Syndrome, 5, 75, 2013.
BIBI, S. & SAKATA, K. Current Status Of Computer-Aided Drug Design For Type 2 Diabetes. Current Computer-Aided Drug Design, 12, 167-177, 2016.
BOUKARAI, Y.; KHALIL, F.; & BOUACHRINE, M. Qsar Study Of Flavonoid Derivatives As In Vitro Inhibitors Agents Of Aldose Reductase (Alr2) Enzyme For Diabetic Complications, 2017.
JALALI-HERAVI, M.; & KYANI, A. Use Of Computer-Assisted Methods For The Modeling Of The Retention Time Of A Variety Of Volatile Organic Compounds: A Pca-Mlr-Ann Approach. Journal Of Chemical Information And Computer Sciences, 44, 1328-1335, 2004.
KAVITHA, S.; KANNAN, K.; & GNANAVEL, S. Synthesis, Characterization And Biological Evaluation Of Novel 2, 5 Substituted-1, 3, 4 Oxadiazole Derivatives. Saudi Pharmaceutical Journal, 25, 337-345, 2017.
KHAN, K. M.; RAHIM, F.; WADOOD, A.; KOSAR, N.; TAHA, M.; LALANI, S.; KHAN, A.; FAKHRI, M. I.; JUNAID, M.; & REHMAN, W. Synthesis And Molecular Docking Studies Of Potent ?-Glucosidase Inhibitors Based On Biscoumarin Skeleton. European Journal Of Medicinal Chemistry, 81, 245-252, 2014.
LI, W.; ZHENG, H.; BUKURU, J.; & DE KIMPE, N. Natural Medicines Used In The Traditional Chinese Medical System For Therapy Of Diabetes Mellitus. Journal Of Ethnopharmacology, 92, 1-21, 2004.
TAHA, M.; ISMAIL, N. H.; LALANI, S.; FATMI, M. Q.; SIDDIQUI, S.; KHAN, K. M.; IMRAN, S.; & CHOUDHARY, M. I. Synthesis Of Novel Inhibitors Of ?-Glucosidase Based On The Benzothiazole Skeleton Containing Benzohydrazide Moiety And Their Molecular Docking Studies. European Journal Of Medicinal Chemistry, 92, 387-400, 2015.
TALELE, T. T.; KHEDKAR, S. A.; & RIGBY, A. C. Successful Applications Of Computer-Aided Drug Discovery: Moving Drugs From Concept To The Clinic. Current Topics In Medicinal Chemistry, 10, 127-141, 2010.
TROPSHA, A.; GRAMATICA, P.; & GOMBAR, V. K. The Importance Of Being Earnest: Validation Is The Absolute Essential For Successful Application And Interpretation Of Qspr Models. Molecular Informatics, 22, 69-77, 2003.
TROTT, O.; & OLSON, A. J. Autodock Vina: Improving The Speed And Accuracy Of Docking With A New Scoring Function, Efficient Optimization, And Multithreading. Journal Of Computational Chemistry, 31, 455-461, 2010.
VEERASAMY, R.; RAJAK, H.; JAIN, A.; SIVADASAN, S.; VARGHESE, C. P.; & AGRAWAL, R. K. Validation Of Qsar Models-Strategies And Importance. International Journal Of Drug Design & Discovery, 3, 511-519, 2011.
WANG, G.; PENG, Z.; WANG, J.; LI, J.; & LI, X. Synthesis And Biological Evaluation Of Novel 2, 4, 5-Triarylimidazole–1, 2, 3-Triazole Derivatives Via Click Chemistry As ?-Glucosidase Inhibitors. Bioorganic & Medicinal Chemistry Letters, 26, 5719-5723, 2016a.
WANG, G.; PENG, Z.; WANG, J.; LI, J.; & LI, X. Synthesis, Biological Evaluation And Molecular Docking Study Of N-Arylbenzo [D] Oxazole-2-Amines As Potential ?-Glucosidase Inhibitors. Bioorganic & Medicinal Chemistry, 24, 5374-5379, 2016b.
ZAWAWI, N. K. N. A.; TAHA, M.; AHMAT, N.; ISMAIL, N. H.; WADOOD, A.; RAHIM, F.; & REHMAN, A. U. Synthesis, In Vitro Evaluation And Molecular Docking Studies Of Biscoumarin Thiourea As A New Inhibitor Of ?-Glucosidases. Bioorganic Chemistry, 63, 36-44, 2015.