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Year 2024, , 591 - 597, 30.09.2024

Bilge Bıçak

https://doi.org/10.17776/csj.1483156

Abstract

References

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  • [2] Hussain, G., Rasul, A., Anwar, H., Aziz, N., Razzaq, A., Wei, W., Ali, M., Li, J., Li, X., Role of plant derived alkaloids and their mechanism in neurodegenerative disorders, Int. J. Biol. Sci., 14(3) (2018) 341.
  • [3] Ng, Y.P., T.C.T. Or, N.Y. Ip, Plant alkaloids as drug leads for Alzheimer's disease, Neurochem. Int., 89 (2015) 260-270.
  • [4] Račková, L., Májeková, M., Košt’álová, D., Štefek, M., Antiradical and antioxidant activities of alkaloids isolated from Mahonia aquifolium. Structural aspects, Bioorg. Med. Chem., 12(17) (2004) 4709-4715.
  • [5] Rehman, S., Khan H., Advances in antioxidant potential of natural alkaloids, Curr. Bioact. Compd., 13(2) (2017) 101-108.
  • [6] Tamariz, J., Burgueño-Tapia, E., Vázquez, M. A., & Delgado, F., Pyrrolizidine alkaloids. The alkaloids: chemistry and biology, 80 (2018) 1-314.
  • [7] Allgaier, C., Franz S., Risk assessment on the use of herbal medicinal products containing pyrrolizidine alkaloids, Regul. Toxicol. Pharmacol., 73(2) (2015) 494-500.
  • [8] Wang, W., Jin, J., Xu, H., Shi, Y., Boersch, M., Yin, Y., Comparative analysis of the main medicinal substances and applications of Echium vulgare L. and Echium plantagineum L.: A review, J. Ethnopharmacol., 285 (2022) 114894.
  • [9] Wei, X., Ruan W., Vrieling K., Current knowledge and perspectives of pyrrolizidine alkaloids in pharmacological applications: A mini-review, Mol., 26(7) (2021) 1970.
  • [10] Schmeller, T., El-Shazly A., Wink M., Allelochemical activities of pyrrolizidine alkaloids: interactions with neuroreceptors and acetylcholine related enzymes, J. Chem. Ecol., 23 (1997) 399-416.
  • [11] Frisch, M., et al., Gaussian 09, Revision A. 1. Gaussian Inc., Wallingford. CT., (2009).
  • [12] Raves, M.L., Harel, M., Pang, Y. P., Silman, I., Kozikowski, A.P., & Sussman, J.L., Structure of acetylcholinesterase complexed with the nootropic alkaloid,(–)-huperzine A, Nat. Struct. Mol. Biol., 4(1) (1997) 57-63.
  • [13] Trott, O., Olson A.J., AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem., 31(2) (2010) 455-461.
  • [14] Biovia, D.S., Discovery studio. Dassault Systèmes BIOVIA, (2016).
  • [15] Daina, A., Michielin O., Zoete V., SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep., 7(1) (2017) 42717.
  • [16] Pires, D.E., Blundell T.L., Ascher D.B., pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures, J. Med. Chem., 58(9) (2015) 4066-4072.
  • [17] Haroon, M., Khalid, M., Shahzadi, K., Akhtar, T., Saba, S., Rafique, J., ... & Imran, M., Alkyl 2-(2-(arylidene) alkylhydrazinyl) thiazole-4-carboxylates: Synthesis, acetyl cholinesterase inhibition and docking studies, J. Mol. Struct., 1245 (2021) 131063.
  • [18] Ali, M.R., Sadoqi, M., Møller, S.G., Boutajangout, A., Mezei, M., Assessing the binding of cholinesterase inhibitors by docking and molecular dynamics studies, J. Mol. Graph. Model., 76 (2017) 36-42.
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  • [21] Vélez, L.A., Delgado, Y., Ferrer-Acosta, Y., Suárez-Arroyo, I.J., Rodríguez, P., & Pérez, D., Theoretical Calculations and Analysis Method of the Physicochemical Properties of Phytochemicals to Predict Gastrointestinal Absorption, (2022).
  • [22] Abouzied, A.S., Break, M., Huwaimel, B., Hussein, W., Alafnan, A., Younes, K., ... & Abouzied, A., Discovery of a novel synthetic thiazole-benzimidazole conjugate that acts as a potent pancreatic lipase inhibitor using in silico and in vitro approaches, Indian J. Pharm. Educ. Res, 57(1) (2023) 218-227.
  • [23] Vlad, I.M., Nuta, D.C., Chirita, C., Caproiu, M.T., Draghici, C., Dumitrascu, F., ... & Limban, C., In Silico and In Vitro Experimental Studies of New Dibenz [b, e] oxepin-11 (6 H) one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents, Mol., 25(2) (2020) 321.
  • [24] Craciun, D., Modra D., Isvoran A., ADME-Tox profiles of some food additives and pesticides, in AIP Conference Proceedings. (2015).
  • [25] Egan, W.J., Merz K.M., Baldwin J.J., Prediction of drug absorption using multivariate statistics, J. Med. Chem., 43(21) (2000) 3867-3877.
  • [26] Muegge, I., Heald S.L., Brittelli D., Simple selection criteria for drug-like chemical matter, J. Med. Chem., 44(12) (2001) 1841-1846.
  • [27] Lin, J.H., Yamazaki M., Role of P-glycoprotein in pharmacokinetics: clinical implications, Clin. Pharmacokinet., 42 (2003) 59-98.
  • [28] Smith, L., Culvenor C., Plant sources of hepatotoxic pyrrolizidine alkaloids, J. Nat. Prod., 44(2) (1981) 129-152.

Geometry Optimization, Molecular Docking and ADMET Studies of Echimidine Molecule

Year 2024, , 591 - 597, 30.09.2024

Bilge Bıçak

https://doi.org/10.17776/csj.1483156

Abstract

Plants are an important food group that has been used as a source of nutrition and healing from past to present. Plants contain secondary metabolites that are still under investigation in drug development studies. Alkaloids, which are secondary metabolites, have antioxidant and antibacterial properties as well as therapeutic potential in various diseases such as Alzheimer's disease. Acetylcholinesterase (AChE) inhibitors come to the fore in the treatment strategy of Alzheimer's disease. Echimidine, a pyrrolizidine alkaloid, is an important compound known to be active in AChE inhibition. Molecular docking method has an important place in elucidating biochemical processes by examining the interactions of drugs or drug candidates with the receptors targeted for the disease. Additionally, information on the absorption, distribution, metabolism, excretion, and toxicity (ADMET) of drug candidate molecules is important in drug development studies. In this study, echimidine molecule was optimized, the molecular docking study was carried out with AChE and the interaction types, binding profile, and binding affinity of echimidine was determined. ADMET analysis of echimidine was also realized to estimate its drug potential. With this study, geometry optimization of the molecule, elucidation of its interactions with AChE, and prediction of its pharmacokinetic properties were achieved for the first time.

Keywords

Echimidine Acetylcholinesterase Molecular docking ADMET

Thanks

I would like to thank the editor and referees for their contributions to the review and evaluation of the manuscript.

References

  • [1] Debnath, B., Singh, W.S., Das, M., Goswami, S., Singh, M.K., Maiti, D., Manna, K., Role of plant alkaloids on human health: A review of biological activities, Mater. Today Chem., 9 (2018) 56-72.
  • [2] Hussain, G., Rasul, A., Anwar, H., Aziz, N., Razzaq, A., Wei, W., Ali, M., Li, J., Li, X., Role of plant derived alkaloids and their mechanism in neurodegenerative disorders, Int. J. Biol. Sci., 14(3) (2018) 341.
  • [3] Ng, Y.P., T.C.T. Or, N.Y. Ip, Plant alkaloids as drug leads for Alzheimer's disease, Neurochem. Int., 89 (2015) 260-270.
  • [4] Račková, L., Májeková, M., Košt’álová, D., Štefek, M., Antiradical and antioxidant activities of alkaloids isolated from Mahonia aquifolium. Structural aspects, Bioorg. Med. Chem., 12(17) (2004) 4709-4715.
  • [5] Rehman, S., Khan H., Advances in antioxidant potential of natural alkaloids, Curr. Bioact. Compd., 13(2) (2017) 101-108.
  • [6] Tamariz, J., Burgueño-Tapia, E., Vázquez, M. A., & Delgado, F., Pyrrolizidine alkaloids. The alkaloids: chemistry and biology, 80 (2018) 1-314.
  • [7] Allgaier, C., Franz S., Risk assessment on the use of herbal medicinal products containing pyrrolizidine alkaloids, Regul. Toxicol. Pharmacol., 73(2) (2015) 494-500.
  • [8] Wang, W., Jin, J., Xu, H., Shi, Y., Boersch, M., Yin, Y., Comparative analysis of the main medicinal substances and applications of Echium vulgare L. and Echium plantagineum L.: A review, J. Ethnopharmacol., 285 (2022) 114894.
  • [9] Wei, X., Ruan W., Vrieling K., Current knowledge and perspectives of pyrrolizidine alkaloids in pharmacological applications: A mini-review, Mol., 26(7) (2021) 1970.
  • [10] Schmeller, T., El-Shazly A., Wink M., Allelochemical activities of pyrrolizidine alkaloids: interactions with neuroreceptors and acetylcholine related enzymes, J. Chem. Ecol., 23 (1997) 399-416.
  • [11] Frisch, M., et al., Gaussian 09, Revision A. 1. Gaussian Inc., Wallingford. CT., (2009).
  • [12] Raves, M.L., Harel, M., Pang, Y. P., Silman, I., Kozikowski, A.P., & Sussman, J.L., Structure of acetylcholinesterase complexed with the nootropic alkaloid,(–)-huperzine A, Nat. Struct. Mol. Biol., 4(1) (1997) 57-63.
  • [13] Trott, O., Olson A.J., AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem., 31(2) (2010) 455-461.
  • [14] Biovia, D.S., Discovery studio. Dassault Systèmes BIOVIA, (2016).
  • [15] Daina, A., Michielin O., Zoete V., SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep., 7(1) (2017) 42717.
  • [16] Pires, D.E., Blundell T.L., Ascher D.B., pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures, J. Med. Chem., 58(9) (2015) 4066-4072.
  • [17] Haroon, M., Khalid, M., Shahzadi, K., Akhtar, T., Saba, S., Rafique, J., ... & Imran, M., Alkyl 2-(2-(arylidene) alkylhydrazinyl) thiazole-4-carboxylates: Synthesis, acetyl cholinesterase inhibition and docking studies, J. Mol. Struct., 1245 (2021) 131063.
  • [18] Ali, M.R., Sadoqi, M., Møller, S.G., Boutajangout, A., Mezei, M., Assessing the binding of cholinesterase inhibitors by docking and molecular dynamics studies, J. Mol. Graph. Model., 76 (2017) 36-42.
  • [19] Lipinski, C.A., Lead-and drug-like compounds: the rule-of-five revolution, Drug Discov. Today Technol., 1(4) (2004) 337-341.
  • [20] Ghose, A.K., Viswanadhan V.N., Wendoloski J.J., A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases, J. Comb. Chem., 1(1) (1999) 55-68.
  • [21] Vélez, L.A., Delgado, Y., Ferrer-Acosta, Y., Suárez-Arroyo, I.J., Rodríguez, P., & Pérez, D., Theoretical Calculations and Analysis Method of the Physicochemical Properties of Phytochemicals to Predict Gastrointestinal Absorption, (2022).
  • [22] Abouzied, A.S., Break, M., Huwaimel, B., Hussein, W., Alafnan, A., Younes, K., ... & Abouzied, A., Discovery of a novel synthetic thiazole-benzimidazole conjugate that acts as a potent pancreatic lipase inhibitor using in silico and in vitro approaches, Indian J. Pharm. Educ. Res, 57(1) (2023) 218-227.
  • [23] Vlad, I.M., Nuta, D.C., Chirita, C., Caproiu, M.T., Draghici, C., Dumitrascu, F., ... & Limban, C., In Silico and In Vitro Experimental Studies of New Dibenz [b, e] oxepin-11 (6 H) one O-(arylcarbamoyl)-oximes Designed as Potential Antimicrobial Agents, Mol., 25(2) (2020) 321.
  • [24] Craciun, D., Modra D., Isvoran A., ADME-Tox profiles of some food additives and pesticides, in AIP Conference Proceedings. (2015).
  • [25] Egan, W.J., Merz K.M., Baldwin J.J., Prediction of drug absorption using multivariate statistics, J. Med. Chem., 43(21) (2000) 3867-3877.
  • [26] Muegge, I., Heald S.L., Brittelli D., Simple selection criteria for drug-like chemical matter, J. Med. Chem., 44(12) (2001) 1841-1846.
  • [27] Lin, J.H., Yamazaki M., Role of P-glycoprotein in pharmacokinetics: clinical implications, Clin. Pharmacokinet., 42 (2003) 59-98.
  • [28] Smith, L., Culvenor C., Plant sources of hepatotoxic pyrrolizidine alkaloids, J. Nat. Prod., 44(2) (1981) 129-152.
There are 28 citations in total.

Details

Primary Language English
Subjects Atomic and Molecular Physics
Journal Section Natural Sciences
Authors

Bilge Bıçak 0000-0003-1147-006X

Publication Date September 30, 2024
Submission Date May 13, 2024
Acceptance Date August 12, 2024
Published in Issue Year 2024

Cite

APA Bıçak, B. (2024). Geometry Optimization, Molecular Docking and ADMET Studies of Echimidine Molecule. Cumhuriyet Science Journal, 45(3), 591-597. https://doi.org/10.17776/csj.1483156