Computational Insights in Drug-likeness and ADMT Properties of -dienes Resemble of Geranial

Yıl 2023, , 174 - 192, 31.12.2023

Goncagül Serdaroğlu

https://doi.org/10.54370/ordubtd.1308195

Öz

This research aims to analyze the drug development potential of geranial, a naturally occurring compound known for its medicinal properties, through in-depth ADMT (Absorption, Distribution, Metabolism, and Toxicity) profiling and Density Functional Theory (DFT) calculations, at B3LYP/6-311G** level and basis set. The optimized and confirmed structures of the data set were used for further computations. The FMO "Frontier Molecular Orbital" energies and MEP "Molecular Electrostatic Potential" were considered to elucidate the possible reactivity features and regions of the molecules, respectively. Concurrently, DFT calculations helped to elucidate the compound's electronic properties and structural stability, further affirming its suitability for drug development. These findings emphasize the potential of compounds structurally related to geranial in the pharmaceutical field and underline the necessity of similar evaluations for novel drug candidates, ensuring safety and efficacy while mitigating potential risks to human health and the environment.

Anahtar Kelimeler

Gerenial, ADMET study, DFT computations

Geranial benzeri -dienlerin İlaç Benzerliği ve ADMT Özelliklerine İlişkin Hesaplamalı Analizler

Öz

Bu araştırma, tıbbi özellikleriyle bilinen, doğal olarak oluşan bir bileşik olan geranialin (sardunya) ilaç geliştirme potansiyelini, derinlemesine ADMT (Absorbsiyon, Dağıtım, Metabolizma ve Toksisite) profili oluşturma ve B3LYP/6-311G** fonksiyon ve temel setinde, Yoğunluk Fonksiyonel Teorisi (DFT) hesaplamaları yoluyla analiz etmeyi amaçlamaktadır. Veri setinin optimize edilmiş ve onaylanmış yapıları daha sonraki hesaplamalar için kullanıldı. FMO "Frontier Molecular Orbital" enerjileri ve MEP "Moleküler Elektrostatik Potansiyel" sırasıyla moleküllerin olası reaktivite özelliklerini ve bölgelerini aydınlatacak şekilde değerlendirildi. Ayrıca, DFT hesaplamaları bileşiğin elektronik özelliklerinin ve yapısal stabilitesinin aydınlatılmasına yardımcı oldu ve ilaç geliştirmeye uygunluğunu doğruladı. Bu bulgular, farmasötik alanda geranial ile yapısal olarak ilişkili bileşiklerin potansiyelini vurgulamakta ve insan sağlığına ve çevreye yönelik potansiyel riskleri azaltırken güvenlik ve etkinliği sağlayan yeni ilaç adayları için benzer değerlendirmelerin gerekliliğinin altını çizmektedir.

Anahtar Kelimeler

Gerenial, ADMT çalışması, DFT hesaplamaları

Kaynakça

• Adorjan, B., & Buchbauer, G. (2010). Biological properties of essential oils: An updated review. Flavour and Fragrance Journal. 25(6), 407-426. 4https://doi.org/10.1002/ffj.2024
• Ali, J., Camilleri, P., Brown, M. B., Hutt, A. J., & Kirton, S. B. (2012). In silico prediction of aqueous solubility using simple QSPR models: The importance of phenol and phenol-like moieties. Journal of Chemical Information and Modeling, 52, 2950−2957. https://doi.org/10.1021/ci300447c
• Bailly, C. (2020). Targets and pathways involved in the antitumor activity of citral and its stereo-isomers. European Journal of Pharmacology, 871, 172945. https://doi.org/10.1016/j.ejphar.2020.172945
• Balusamy, S. R., Perumalsamy, H., Veerappan, K., Huq, M. A., Rajeshkumar, S., Lakshmi, T., & Kim, Y. J. (2020). Citral induced apoptosis through modulation of key genes involved in fatty acid biosynthesis in human prostate cancer cells: In silico and in vitro study. BioMed Research International, 2020, 6040727. https://doi.org/10.1155/2020/6040727
• Becke, A. D. (1993). A new mixing of Hartree–Fock and local density‐functional theories. Journal of Chemical Physics, 98, 1372-1377. https://doi.org/10.1063/1.464304
• Bouyahya, A., Guaouguaou, F. E., El Omari, N., El Menyiy, N., Balahbib, A., El-Shazly, M., & Bakri, Y. (2022). Anti-inflammatory and analgesic properties of Moroccan medicinal plants: Phytochemistry, in vitro and in vivo investigations, mechanism insights, clinical evidences and perspectives. Journal of Pharmaceutical Analysis, 12(1), 35-57. https://doi.org/10.1016/j.jpha.2021.07.004
• Burdock, G. A., & Carabin, I. G. (2009). Safety assessment of coriander (Coriandrum sativum L.) essential oil as a food ingredient. Food and Chemical Toxicology, 47(6), 1202-1209. https://doi.org/10.1016/j.fct.2008.11.006
• Carpenter, J. F., Pikal, M. J., Chang, B. S., & Randolph, T. W. (1997). Rational design of stable lyophilized protein formulations: Theory and practice. In Pharmaceutical Biotechnology, 9, 189-227. https://doi.org/10.1023/A:1012180707283
• Cheng, T., Zhao, Y., Li, X., Lin, F., Xu, Y., Zhang, X., Li, Y., & Wang, R. (2007). Computation of octanol−water partition coefficients by guiding an additive model with knowledge. Journal of Chemical Information and Modeling, 47(6), 2140–2148. https://doi.org/10.1021/ci700257y
• Daina, A., Michielin, O., & Zoete, V. (2014). iLOGP: A simple, robust, and efficient description of n‑octanol/water partition coefficient for drug design using the GB/SA approach. Journal of Chemical Information and Modeling, 54(12), 3284–3301. https://doi.org/10.1021/ci500467k
• Daina, A., Michielin, O., & Zoete, V. (2017). SwissADME: A free web tool to evaluate pharmacokinetics, druglikeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7, 42717. https://doi.org/10.1038/srep42717
• Delaney, J. S. (2004). ESOL: Estimating aqueous solubility directly from molecular structure. Journal of Chemical Information and Computer Sciences, 44, 1000-1005. https://doi.org/10.1021/ci034243x
• Dennington, R., Keith, T. A., & Millam, J. M. (2016). GaussView, version 6.0.16. Semichem Inc Shawnee Mission KS. Egan, W. J., Merz, K. M., Jr., & Baldwin, J. J. (2000). Prediction of drug absorption using multivariate statistics. Journal of Medicinal Chemistry, 43, 3867-3877. https://doi.org/10.1021/jm000292e
• Erdogan, M., & Serdaroglu, G. (2021). New Hybrid (E)-4-((pyren-1-ylmethylene)amino)-N-(thiazol-2-yl)benzenesulfonamide as a potential drug candidate: Spectroscopy, TD-DFT, NBO, FMO, and MEP studies. Chemistry Select, 6, 9369–9381. https://doi.org/10.1002/slct.202102602
• Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G. A., Nakatsuji, H., Caricato, M., Li, X., Hratchian, H. P., Izmaylov, A. F., Bloino, J., Zheng, G., Sonnenberg, J. L., Hada, M., Ehara, … Fox, D. J. (2013). Gaussian 09W, Revision D.01. Gaussian Inc.
• Gaonkar, R., Yallappa, S., Dhananjayac, B. L., & Hegde, G. (2016). Development and validation of reverse phase high-performance liquid chromatography for citral analysis from essential oils. Journal of Chromatography B, 1036–1037, 50–56. https://doi.org/10.1016/j.jchromb.2016.10.001
• Gazquez, J. L., Cedillo, A., & Vela, A. (2007). Electrodonatingand Electroaccepting Powers. Journal of Physical Chemistry A, 111(10), 1966-1970. https://doi.org/10.1021/jp065459f
• Ghose, A. K., Viswanadhan, V. N., & Wendoloski, J. J. (1999). A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases. Journal of Combinatorial Chemistry, 1, 55-68. https://doi.org/10.1021/cc9800071
• Gomez, B., Likhanova, N. V., Domínguez-Aguilar, M. A., Martínez-Palou, R., Vela, A., & Gazquez, J. L. (2006). Quantum chemical study of the inhibitive properties of 2-Pyridyl-Azoles. Journal of Physical Chemistry B, 110(18), 8928-8934. https://doi.org/10.1021/jp057143y
• Herzberg, G. (1964). Molecular spectra and molecular structure III (1st ed.). D. Van Nostrand Company Inc.
• Hill, T. L. (1962). An introduction to statistical thermodynamics. Addison-Wesley Publishing.
• Hsissou, R., Benhiba, F., Echihi, S., Benzidia, B., Cherrouf, S., Haldhar, R., Alvi, P. A., Kaya, S., Serdaroglu, G., & Zarrouk, A. (2021). Performance of curing epoxy resin as potential anticorrosive coating for carbon steel in 3.5% NaCl medium: Combining experimental and computational approaches. Chemical Physics Letters, 783, 139081. https://doi.org/10.1016/j.cplett.2021.139081
• Jackson, E., Shoemaker, R., Larian, N., & Cassis, L. (2017). Adipose tissue as a site of toxin accumulation. Comprehensive Physiology, 7(4), 1085–1135. https://doi.org/10.1002/cphy.c160038
• Janak, J. F. (1978). Proof that ∂E/∂ni=εin density-functional theory. Physical Review B, 18(12), 7165-7168. https://doi.org/10.1103/PhysRevB.18.7165
• Ju, J., Xie, Y., Yu, H., Guo, Y., Cheng, Y., Qian, H., & Yao, W. (2020). Analysis of the synergistic antifungal mechanism of eugenol and citral. LWT, 123, 109128. https://doi.org/10.1016/j.lwt.2020.109128
• Koopmans, T. (1934). Über die zuordnung von wellenfunktionen und eigenwertenzu den einzelnen elektronen eines atoms. Physica, 1, 104-113. https://doi.org/10.1016/S0031-8914(34)90011-2
• Kudin, K. N., Scuseria, G. E., & Cancès, E. (2002). A black-box self-consistent field convergence algorithm: One step closer. Journal of Chemical Physics, 116(19), 8255-8261. https://doi.org/10.1063/1.1470195
• Lee, C., Yang, W., & Parr, R. G. (1988). Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Physical Review B, 37, 785-789. https://doi.org/10.1103/PhysRevB.37.785
• Li, R. Y., Wu, X. M., Yin, X. H., Long, Y. H., & Li, M. (2015). Naturally produced citral can significantly inhibit normal physiology and induce cytotoxicity on Magnaporthe grisea. Pesticide Biochemistry and Physiology, 118, 19-25. https://doi.org/10.1016/j.pestbp.2014.10.015
• Li, X., & Frisch, M. J. (2006). Energy-represented DIIS within a hybrid geometry optimization method. Journal of Chemical Theory and Computation, 2(3), 835-839. https://doi.org/10.1021/ct050275a
• Lin, J. H., & Lu, A. Y. (1997). Role of Pharmacokinetics and Metabolism in Drug Discovery and Development. Pharmacological Reviews, 49(4), 403-449. https://www.ncbi.nlm.nih.gov/pubmed/9443165
• Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001). Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews, 46, 3–26. https://doi.org/10.1016/S0169-409X(00)00129-0
• Martin, Y. C. (2005). A bioavailability score. Journal of Medicinal Chemistry, 48, 3164-3170. https://doi.org/10.1021/jm0492002
• McGeer, J. C., Brix, K. V., Skeaff, J. M., DeForest, D. K., Brigham, S. I., Adams, W. J., & Green, A. (2003). Inverse relationship between bioconcentration factor and exposure concentration for metals: implications for hazard assessment of metals in the aquatic environment. Environmental Toxicology and Chemistry, 22(5), 1017-1037. https://doi.org/10.1002/etc.5620220509
• McLean, A. D., & Chandler, G. S. (1980). Contracted Gaussian-basis sets for molecular calculations. 1. 2nd row atoms, Z=11-18. Journal of Chemical Physics, 72(9), 5639-5648. https://doi.org/10.1063/1.438980
• McQuarrie, D. A. (1973). Statistical thermodynamics. Harper & Row Publishers. Muegge, I., Heald, S. L., & Brittelli, D. (2001). Simple selection criteria for drug-like chemical matter. Journal of Medicinal Chemistry, 44(12), 1841–1846. https://doi.org/10.1021/jm015507e
• Nendza, M., & Müller, M. (2010). Screening for low aquatic bioaccumulation. 1. Lipinski’s ‘Rule of 5’ and molecular size. SAR and QSAR in Environmental Research, 21(5-6), 495-512. https://doi.org/10.1080/1062936X.2010.502295
• Oladeji, O. S., Oluyori, A. P., Bankole, D. T., & Afolabi, T. Y. (2020). Natural products as sources of antimalarial drugs: Ethnobotanical and ethnopharmacological studies. BioMed Research International, 2020, 7076139. https://doi.org/10.1155/2020/7076139
• Ortiz, M. I., González-García, M. P., Ponce-Monter, H. A., Castañeda-Hernández, G., & Aguilar-Robles, P. (2010). Synergistic effect of the interaction between naproxen and citral on inflammation in rats. Phytomedicine, 18(1), 74-79. https://doi.org/10.1016/j.phymed.2010.05.009
• Oyedeji, A. O., Okunowo, W. O., Osuntoki, A. A., Olabode, T. B., & Ayo-folorunso, F. (2020). Insecticidal and biochemical activity of essential oil from Citrus sinensis peel and constituents on Callosobrunchus maculatus and Sitophilus zeamais. Pesticide Biochemistry and Physiology, 168, 104643. https://doi.org/10.1016/j.pestbp.2020.104643
• Parr, R. G., & Pearson, R. G. (1983). Absolute hardness: companion parameter to absolute electronegativity. Journal of the American Chemical Society, 105, 7512-7516. https://doi.org/10.1021/ja00364a005
• Parr, R. G., Szentpaly, L. V., & Liu, S. (1999). Electrophilicity index. Journal of the American Chemical Society, 121, 1922-1924. https://doi.org/10.1021/ja983494x
• Pearson, R. G. (1986). Absolute electronegativity and hardness correlated with molecular orbital theory. Proceedings of the National Academy of Sciences of the United States of America, 83, 8440-8441. https://doi.org/10.1073/pnas.83.22.8440
• Perdew, J. P., & Levy, M. (1983). Physical content of the exact Kohn-Sham orbital energies: Band gaps and derivative discontinuities. Physical Review Letters, 51(20), 1884-1887. https://doi.org/10.1103/PhysRevLett.51.1884
• Perdew, J. P., Parr, R. G., Levy, M., & Balduz, J. L. (1982). Density-functional theory for fractional particle number: Derivative discontinuities of the energy. Physical Review Letters, 49(23), 1691-1694. https://doi.org/10.1103/PhysRevLett.49.1691
• Plata-Rueda, A., Martínez, L. C., da Silva Rolim, G., Pereira Coelho, R., Henrique Santos, M., de Souza Tavares, W., Cola Zanuncio, J., & Serrão, J. E. (2020). Insecticidal and repellent activities of Cymbopogon citratus (Poaceae) essential oil and its terpenoids (citral and geranyl acetate) against Ulomoides dermestoides. Crop Protection, 137, 105299. https://doi.org/10.1016/j.cropro.2020.105299
• Raghavachari, K., Binkley, J. S., Seeger, R., & Pople, J. A. (1980). Self-Consistent Molecular Orbital Methods. 20. Basis set for correlated wave-functions. Journal of Chemical Physics, 72(1), 650-654. https://doi.org/10.1063/1.438955
• Ruiz Perez-Cacho, P., & Rouseff, R. (2008). Processing and storage effects on orange juice aroma: A review. Journal of Agricultural and Food Chemistry, 56(21), 9785-9796. https://doi.org/10.1021/jf801244j
• Samarghandian, S., Shoshtari, M. E., Sargolzaei, J., Hossinimoghadam, H., & Azad Farahzad, J. (2014). Anti-tumor activity of safranal against neuroblastoma cells. Pharmacognosy Magazine, 10(Suppl 2), S419-S424. https://doi.org/10.4103/0973-1296.133296
• Serdaroğlu, G. (2011). A DFT study of determination of the reactive sites of the acetylcholine and its agonists: In the gas phase and dielectric medium. International Journal of Quantum Chemistry, 111(10) 2464-2475. https://doi.org/10.1002/qua.22512
• Serdaroğlu, G. (2011). DFT and Ab initio computational study on the reactivity sites of the GABA and its agonists, such as CACA, TACA, DABA, and muscimol: In the gas phase and dielectric media. International Journal of Quantum Chemistry, 111(14), 3938-3948. https://doi.org/10.1002/qua.22809
• Serdaroglu, G., & Durmaz, S. (2010). DFT and statistical mechanics entropy calculations of diatomic and polyatomic molecules. Indian Journal of Chemistry, 49, 861-866. http://nopr.niscpr.res.in/handle/123456789/9918
• Serdaroğlu, G., & Ortiz, J. V. (2017). Ab initio calculations on some antiepileptic drugs such as phenytoin, phenbarbital, ethosuximide and carbamazepine. Structural Chemistry, 28(4), 957-964. https://doi.org/10.1007/s11224-016-0898-3
• Serin, S. (2022). DFT-based computations on some structurally related N-substituted piperazine. Journal of the Indian Chemical Society, 99, 100766. https://doi.org/10.1016/j.jics.2022.100766
• Serin, S. (2023). A comprehensive DFT study on organosilicon-derived fungicide flusilazole and its germanium analogue: A computational approach to Si/Ge bioisosterism. Journal of the Indian Chemical Society, 100, 100939. https://doi.org/10.1016/j.jics.2023.100939
• Serin, S., Kaya, G., & Utku, T. (2022). Insights into solvent effects on molecular properties, physicochemical parameters, and NLO behavior of brinzolamide, a bioactive sulfonamide: A computational study. Journal of the Indian Chemical Society, 99, 100738. https://doi.org/10.1016/j.jics.2022.100738
• Sharma, A. D., & Kaur, I. (2023). Targeting penicillin binding proteins (PBPs) by using bioactive geranial from essential oil of Cymbopogan pendulus against gram-positive and gram-negative bacteria: Molecular docking and experimental approach. Bulgarian Chemical Communications, 55(1), 40-47. http://www.bcc.bas.bg/BCC_Volumes/Volume_55_Number_1_2023/bcc-55-1-2023.pdf#page=38
• Sharmeen, J. B., Mahomoodally, F. M., Zengin, G., & Maggi, F. (2021). Essential oils as natural sources of fragrance compounds for cosmetics and cosmeceuticals. Molecules, 26, 666. https://doi.org/10.3390/molecules26030666
• Silva, B. I. M., Nascimento, E. A., Silva, C. J., et al. (2021). Anticancer activity of monoterpenes: A systematic review. Molecular Biology Reports, 48, 5775-5785. https://doi.org/10.1007/s11033-021-06578-5
• Tchoumbougnang, F., Amvam Zollo, P. H., Dagne, E., & Mekonnen, Y. (2005). In vivo antimalarial activity of essential oils from Cymbopogon citratus and Ocimum gratissimum on mice infected with Plasmodium berghei. Planta Medica, 71(1), 20-23. https://doi.org/10.1055/s-2005-837745
• Veber, D. F., Johnson, S. R., Cheng, H.-Y., Smith, B. R., Ward, K. W., & Kopple, K. D. (2002). Molecular properties that influence the oral bioavailability of drug candidates. Journal of Medicinal Chemistry, 45, 2615-2623. https://doi.org/10.1021/jm020017n
• Viktorová, J., Stupák, M., Rehoˇrov ˇ á, K., Dobiasová, S., Hoang, L., Hajšlová, J., Van Thanh, T., Van Tri, L., Van Tuan, N., & Rum, T. (2020). Lemon grass essential oil does not modulate cancer cells multidrug resistance by citral—its dominant and strongly antimicrobial compound. Foods, 9, 585. https://doi.org/10.3390/foods9050585
• Wildman, S. A., & Crippen, G. M. (1999). Prediction of physicochemical parameters by atomic contributions. Journal of Chemical Information and Computer Sciences, 39, 868-873. https://doi.org/10.1021/ci990307l
• Wohlmuth, H., Smith, M. K., Brooks, L. O., Myers, S. P., & Leach, D. N. (2006). Essential oil composition of diploid and tetraploid clones of ginger (Zingiber officinale Roscoe) grown in Australia. Journal of Agricultural and Food Chemistry, 54(4), 1414–1419. https://doi.org/10.1021/jf0521799
• Zeng, R., Zou, X., Huang, C., Si, H., Song, J., Zhang, J., Luo, H., Wang, Z., Wang, P., Fan, G., Rao, X., Liao, S., & Chen, S. (2023). Novel design of citral-thiourea derivatives for enhancing antifungal potential against Colletotrichum gloeosporioides. Journal of Agricultural and Food Chemistry, 71(7), 3173-3183. https://doi.org/10.1021/acs.jafc.2c07851