Study of the Quantitative Structure Activity Relationship (QSAR) of a Series of Molecules Derived from Thioureas with Anticancer Activities in the Liver

Doumbia Siriki; Dembele Georges Stephane; Tuo Nanou Tieba; Konate Bibata; Kodjo Charles; Ziao Nahosse

doi:doi:10.11648/j.sjc.20231103.12

| Peer-Reviewed

Study of the Quantitative Structure Activity Relationship (QSAR) of a Series of Molecules Derived from Thioureas with Anticancer Activities in the Liver

Doumbia Siriki, Dembele Georges Stephane, Tuo Nanou Tieba, Konate Bibata, Kodjo Charles, Ziao Nahosse

Published in Science Journal of Chemistry (Volume 11, Issue 3)

Received: 9 May 2023 Accepted: 27 May 2023 Published: 9 June 2023

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

The study of the quantitative structure activity relationship (QSAR) of liver cancer was carried out using a series of twenty-five (25) molecules derived from thioureas. The molecular descriptors were obtained after optimization of all these molecules at the B3LYP/6-31+ G (d, p) computational level. The multiple linear regression (MLR) method was used to carry out this study. The use of this method has thus made it possible to obtain a model from the molecular descriptors that are the lipophilicity LogP, the bond lengths d(C=N2) and d(N2-Cphen1), the vibration frequency υ (C =O) and the number of atoms. The results of the statistical indicators obtained from the model (R2=0.906; RMCE=0.198; F= 21.170), allow us to say that this model is acceptable, robust and has good predictive power. Also, the vibration frequency of the carbon-oxygen double bond (C=O), the length of the C-N2 bond and the lipophilicity (LogP) were found to be the priority descriptors in the prediction of the anticancer activity of the liver. Moreover, all the criteria of Tropsha et al. were verified by our model. Moreover, the analysis of the domain of applicability of this model shows that a prediction of the anticancer activity of new derivatives of thiourea is acceptable when its leverage value is less than 1.06, otherwise the anticancer activity of the liver of this compound could not be reliably predicted.

Published in	Science Journal of Chemistry (Volume 11, Issue 3)
DOI	10.11648/j.sjc.20231103.12
Page(s)	78-87
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2023. Published by Science Publishing Group

Keywords

QSAR, RML, Thiourea Derivatives, Lipophilia (LogP), Area of Applicability

References

[1]	V. A. Arzumanian, O. I. Kiseleva and E. V. Poveranna, The Curious Case of The HepG2 cell line: 40 years of Expertise; Int. J. Mol Sci., 2021. Dec 4, 22 (23): 13135.
[2]	J. Thusyan, N. S. Wickramatne, K. H., I. Thabrew, S. R. Samarakoon, Cytotoxicity against Human Hepatocellular Carcinoma (HepG2) cells and Antioxydant Activity of Selected Endemic or Medicinal Plants in Sri Lanka, Adv. Pharmacol. Pharm. Sci., 2022, Mar 30, 2022, 6407688974.
[3]	K. D. Miller, L. Nogueira, A. B. Mariotto, J. H. Rowland, K. R. Yabroff, C. M. Alfano, A. Jemal, J. L. Kramer, Cancer treatment and survivorship statitics, C. A. Cancer J. Clin., 2019, 69 (5), 363-385.
[4]	A. Mahapatra, T. Prasad and T. Sharma, Pyrimidine: a review on anticancer activity with key emphasis on SAR, Fut. J. of Pharm. Sci., 2021, 7, 123.
[5]	N. M. Ahmed, M. M. Youns, M. K. Soltan and A. M. Said, Design, Synthesis, N. M. Ahmed, M. M. Youns, M. K. Soltan and A. M. Said, Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitor Activity. Molecules, 2020, 26, 1838.
[6]	H. Zhuang, W. Jiang, W. Cheng et al., Down-regulation of HSP27 sensitizes TRAIL-resistant tumor cell of TRAIL-induce apoptosis, Lung Cancer, 2010, 68, 27-38.
[7]	L. C. Hamming, B., J. Slotmaman, H. M. W. Verheul, Angiogenesis, 2017, 20, 217-232.
[8]	S. Saeed,; N. Rashid,;, P. G Jones.; M. Ali,; R. Hussain,; Eur. J. of Med; Chem.. 2010, 45, 1323-31.
[9]	S. Fortin, Molecular modeling, chemical synthesis, evaluation of antiproliferative activity and determination of mechanism of action of novel hybrid arylchloroethylurea and 2-imidazolidone derivatives, Université de Laval Québec, 2010 p 4.
[10]	B. Werth, The billion dollard molecule, one company’s quest for the perfect drug, 1995, 1.
[11]	M. R. Yadav New drug discovery: Where are you heating to ?, J. Adv. Pharm. Tech. Res. 2020, 4 (1) 2.
[12]	R. Hmamouchi, M. Bouachrine, T. Lakhlifi, Pratique de la Relation Quantitative Structure Activité/Propriété (RQSA / RQSP), Rev. Interdisc., 2016, 1 (1).
[13]	M. Ghamali, S. Chiita, M. Bouachrini, T. Lakhlifi, General methodology of a RQSA/RQSP study, Rev. Interdisc., 2016, 1 (1).
[14]	V. Kumar, S. Chimni, Recent Developments on Thiourea Based Anticancer Chemotherapeutics, Anticancer Agents Med. Chem., 2015, 15, 163-175.
[15]	A. Shakeel, A. A. Altaf, A. M. Qureshi, A. Badshah, Thiourea Derivatives in Drug Design and Medicinal Chemistry: A. Short Review, J. of Drug Med. Chem., 2016, 2, 10-20.
[16]	N. A. Meanwell, Symposis of some Recent Tactical Application of Bioisosteres in Drug Design, J. Mod. Chem., 2011, 54, 2539-2591.
[17]	S. Saeed, N. Rachid: M. Ali, R. Hussain, P. G. Jones, Eur. J. of Chem., 2010, 1 (3), 221-227.
[18]	W. Bai, J. Ji, Q. Huang, Synthesis and evaluation of new thiourea derivatives as antitumor and antiangiogenic agents, Tetrahed. Lett., 2020, 61, 15236,
[19]	P. K. Chattaraj, A. Cedillo et R. G. Parr, J. Phys. Chem., 1991, 103, 7645.
[20]	P. Ayers et M. Levy, «Density Functional Approach to the Frontier-Electron Theory of Chemical Reactivity,» Theorical Chemistry Accounts-springer, 2000, 103 (13-4), 353-360.
[21]	C. Hansch, P. G. Sammes et J. B. Taylor, «in: Comprehensive Medicinal Chemistry,» Computers and the medicinal chemist, 1990, 4, 33-58.
[22]	R. Franke, «Theoretical Drug Design Methods,» Elsevier, 1984.
[23]	M. J. Frisch, G. W. Trucks, H. B. Schlegel, et al. Gaussian 09, Inc., Wallingford CT, 2009.
[24]	Microsoft Excel, «(15.0.4420.1017) MSO (15.0.4420.1017) 64 Bits,» Microsoft Office Professionnel, 2016.
[25]	XLSTAT, « XLSTAT and Addinsoft are Registered Trademarks of Addinsoft,» Copyright Addinsoft, 2014.
[26]	Tammo, Theoretical Analysis of Molecular Membrane Organization, B. Raton, Éd., Florida: CRC, 1995.
[27]	G. W. Snedecor et W. G. Cochran, Methods Statistical, India: Oxford and IBH: New Delhi, 1967, p. 381.
[28]	A. Nayyar, A. Malde, R. Jain, and E. Coutinho, 3D-QSAR study of ring-substituted quinoline class of anti-tuberculosis agents, Bio. & Med. Chem., 2006, 14, 847-856.
[29]	A. Manvar, A. Malde, J. Verma, V. Virsodia, A. Mishra, K. Upadhyay, H. Acharya, E. Coutinho, A. Shah, Synthesis, anti-tubercular activity and 3D-QSAR study of coumarin-4-acetic acid benzylidene hydrazides, Eur. J. of Med. Chem., 2008, 43, 2395-2403.
[30]	M. Song, M. Clark, Development and Evaluation of an in Silico Model for hERG Binding, J. Chem. Inf. Model. 2006, 46, 392-400.
[31]	E. Rutkowska, K. Pajak and K. Jozwiak, Lipophilicity - Methods of Determination and its Role in Medicinal Chemistry, Act. Pol. Pharm. - Drug Res., 2013, 70 (1), 3-18,
[32]	A. Cozma, V. Zaharia, A. Ignat, S. Gocan et N. Grinberg, Prediction of the Lipophilicity of Nine New Synthesized Selenazoly and Three Aroyl–Hydrazinoselenazoles Derivatives by Reversed-Phase High Performance Thin-Layer Chromatography, J. of Chrom. Sci., 2012; 50, 157– 161.
[33]	R. Mannhold, G. I. Poda, C. Ostermann, I. V. Tetko, Calculation of Molecular Lipophilicity: State-of-the-Art and Comparison of LogP Methods on More Than 96,000 Compounds, J. of Pharm. Sci., 2009, 98 (3), 861-893.
[34]	M. A. Bakht, M. F. Alajmi, P. Alam, A. Alam, P. Alam, T. M. Aljarba, Theoretical and experimental study on lipophilicity and wound healing activity of ginger compounds, Asian Pac. J. of Trop. Biomed. 2014; 4 (4): 329-333.
[35]	J. Kujawski, H. Popielarska, A. Myka, B. Drabińska, M. K. Bernard, The logP Parameter as a Molecular Descriptor in the Computer-aided Drug Design - an Overview, Comp. Meth. In Sci. And Techn. 2012, 18 (2), 81-88.
[36]	J. Dearden and A. Worth, In Silico Prediction of Physicochemical Properties, JRC Sci. and techn. Rep., 2015, 19-23.
[37]	Gnewuch CT, Sosnovsky G (2002). Critical appraisals of approaches for predictive designs in anticancer drugs. Cell Mol Life Sci. 59: 959-1023.
[38]	acdlabs, Advanced Chemistry Development / Chemskecht, 1994-2010.
[39]	Guillaume Fayet, Development of a QSPR model for predicting the explosive properties of nitroaromatic compounds, Doctoral thesis, Université Pierre and Marie Curie. 30 Mars 2010, p 63.
[40]	N. J.-B. Kangah, M. G.-R. Koné, C. G. Kodjo, B. R. N’guessan, S. A. Kablan, Yéo et N. Ziao, «Antibacterial Activity of Schiff Bases Derived from Ortho Diaminocyclohexane, Meta-Phenylenediamine and 1,6-Diaminohexane: Qsar Study with Quantum Descriptors,» Int. J. of Pharm. Sci. Inv., 2017. 6 (113), 38-43.
[41]	E. X. Esposito, A. J. Hopfinger et J. D. Madura, «Methods for Applying the Quantitative Structure-Activity Relationship Paradigm» Met. in Mol. Bio. 2004, vol. 275, pp. 131-213.
[42]	L. Eriksson, J. Jaworska, A. Worth, M. D. Cronin, R. M. Mc Dowell et P. Gramatica, «Methods for Reliability and Uncertainty Assessment and for Applicability Evaluations of Classification- and Regression-Based QSARs,» Environmental Health Perspectives, 2003, 111,(110), 1361-1375.
[43]	K. Roy et al. A Primer on QSAR/QSPR Modeling, Chapter 2 Statistical Methods in QSAR/QSPR, Springer. Briefs in Mol. Sci., 2015, pp 37-59.
[44]	R. Veerasamy, H. Rajak, A. Jain, S. Sivadasan, C. P. Varghese et R. K. Agrawal, Validation of QSAR Models - Strategies and Importance International J; of Drug Des; and Disc;, 2011, 2 (3), 511-519.
[45]	M. Shahlaei. Descriptor Selection Methods in Quantitative Structure−Activity Relationship Studies: A Review Study, Chem. Rev., Am. Chem. Soc. Public., 2013.
[46]	T. M. Martin, P. Harten, D. M. Young, E. N. Muratov, A. Golbraikh, H. Zhu and A. Tropsha. Does Rational Selection of Training and Test Sets Improve the Outcome of QSAR Modeling? J. Chem. Inf. Model. 2012, 52, 2570-2578,
[47]	N. N.-Jeliazkova and J. Jaworska. An Approach to Determining Applicability Domains for QSAR Group Contribution Models: An Analysis of SRC KOWWIN, ATLA, 2005, 33, 461–470.
[48]	F. Sahigara, K. Mansouri, D. Ballabio, A. Mauri, V. Consonni and R. Todeschini, Comparison of Different Approaches to Define the Applicability Domain of QSAR Models, Mol. 2012, 17, 4791-4810.
[49]	A. Fortuné, «Molecular Modeling Techniques applied to the Study and Optimization of Immunogenic Molecules and Chemoresistance Modulators. Drugs,» 2006.

Cite This Article

Plain Text BibTeX RIS

APA Style

Doumbia Siriki, Dembele Georges Stephane, Tuo Nanou Tieba, Konate Bibata, Kodjo Charles, et al. (2023). Study of the Quantitative Structure Activity Relationship (QSAR) of a Series of Molecules Derived from Thioureas with Anticancer Activities in the Liver. Science Journal of Chemistry, 11(3), 78-87. https://doi.org/10.11648/j.sjc.20231103.12

Copy | Download

ACS Style

Doumbia Siriki; Dembele Georges Stephane; Tuo Nanou Tieba; Konate Bibata; Kodjo Charles, et al. Study of the Quantitative Structure Activity Relationship (QSAR) of a Series of Molecules Derived from Thioureas with Anticancer Activities in the Liver. Sci. J. Chem. 2023, 11(3), 78-87. doi: 10.11648/j.sjc.20231103.12

Copy | Download

AMA Style

Doumbia Siriki, Dembele Georges Stephane, Tuo Nanou Tieba, Konate Bibata, Kodjo Charles, et al. Study of the Quantitative Structure Activity Relationship (QSAR) of a Series of Molecules Derived from Thioureas with Anticancer Activities in the Liver. Sci J Chem. 2023;11(3):78-87. doi: 10.11648/j.sjc.20231103.12

Copy | Download

@article{10.11648/j.sjc.20231103.12,
  author = {Doumbia Siriki and Dembele Georges Stephane and Tuo Nanou Tieba and Konate Bibata and Kodjo Charles and Ziao Nahosse},
  title = {Study of the Quantitative Structure Activity Relationship (QSAR) of a Series of Molecules Derived from Thioureas with Anticancer Activities in the Liver},
  journal = {Science Journal of Chemistry},
  volume = {11},
  number = {3},
  pages = {78-87},
  doi = {10.11648/j.sjc.20231103.12},
  url = {https://doi.org/10.11648/j.sjc.20231103.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.sjc.20231103.12},
  abstract = {The study of the quantitative structure activity relationship (QSAR) of liver cancer was carried out using a series of twenty-five (25) molecules derived from thioureas. The molecular descriptors were obtained after optimization of all these molecules at the B3LYP/6-31+ G (d, p) computational level. The multiple linear regression (MLR) method was used to carry out this study. The use of this method has thus made it possible to obtain a model from the molecular descriptors that are the lipophilicity LogP, the bond lengths d(C=N2) and d(N2-Cphen1), the vibration frequency υ (C =O) and the number of atoms. The results of the statistical indicators obtained from the model (R2=0.906; RMCE=0.198; F= 21.170), allow us to say that this model is acceptable, robust and has good predictive power. Also, the vibration frequency of the carbon-oxygen double bond (C=O), the length of the C-N2 bond and the lipophilicity (LogP) were found to be the priority descriptors in the prediction of the anticancer activity of the liver. Moreover, all the criteria of Tropsha et al. were verified by our model. Moreover, the analysis of the domain of applicability of this model shows that a prediction of the anticancer activity of new derivatives of thiourea is acceptable when its leverage value is less than 1.06, otherwise the anticancer activity of the liver of this compound could not be reliably predicted.},
 year = {2023}
}

Copy | Download

TY  - JOUR
T1  - Study of the Quantitative Structure Activity Relationship (QSAR) of a Series of Molecules Derived from Thioureas with Anticancer Activities in the Liver
AU  - Doumbia Siriki
AU  - Dembele Georges Stephane
AU  - Tuo Nanou Tieba
AU  - Konate Bibata
AU  - Kodjo Charles
AU  - Ziao Nahosse
Y1  - 2023/06/09
PY  - 2023
N1  - https://doi.org/10.11648/j.sjc.20231103.12
DO  - 10.11648/j.sjc.20231103.12
T2  - Science Journal of Chemistry
JF  - Science Journal of Chemistry
JO  - Science Journal of Chemistry
SP  - 78
EP  - 87
PB  - Science Publishing Group
SN  - 2330-099X
UR  - https://doi.org/10.11648/j.sjc.20231103.12
AB  - The study of the quantitative structure activity relationship (QSAR) of liver cancer was carried out using a series of twenty-five (25) molecules derived from thioureas. The molecular descriptors were obtained after optimization of all these molecules at the B3LYP/6-31+ G (d, p) computational level. The multiple linear regression (MLR) method was used to carry out this study. The use of this method has thus made it possible to obtain a model from the molecular descriptors that are the lipophilicity LogP, the bond lengths d(C=N2) and d(N2-Cphen1), the vibration frequency υ (C =O) and the number of atoms. The results of the statistical indicators obtained from the model (R2=0.906; RMCE=0.198; F= 21.170), allow us to say that this model is acceptable, robust and has good predictive power. Also, the vibration frequency of the carbon-oxygen double bond (C=O), the length of the C-N2 bond and the lipophilicity (LogP) were found to be the priority descriptors in the prediction of the anticancer activity of the liver. Moreover, all the criteria of Tropsha et al. were verified by our model. Moreover, the analysis of the domain of applicability of this model shows that a prediction of the anticancer activity of new derivatives of thiourea is acceptable when its leverage value is less than 1.06, otherwise the anticancer activity of the liver of this compound could not be reliably predicted.
VL  - 11
IS  - 3
ER  -

Copy | Download

Author Information

Doumbia Siriki

Laboratory of Thermodynamics and Physico-Chemistry of the Environment, UFR SFA, Université Nangui Abrogoua, Abidjan, Ivory Coast
Dembele Georges Stephane

Laboratory of Thermodynamics and Physico-Chemistry of the Environment, UFR SFA, Université Nangui Abrogoua, Abidjan, Ivory Coast
Tuo Nanou Tieba

Laboratory of Thermodynamics and Physico-Chemistry of the Environment, UFR SFA, Université Nangui Abrogoua, Abidjan, Ivory Coast
Konate Bibata

Laboratory of Thermodynamics and Physico-Chemistry of the Environment, UFR SFA, Université Nangui Abrogoua, Abidjan, Ivory Coast
Kodjo Charles

Laboratory of Thermodynamics and Physico-Chemistry of the Environment, UFR SFA, Université Nangui Abrogoua, Abidjan, Ivory Coast
Ziao Nahosse

Laboratory of Thermodynamics and Physico-Chemistry of the Environment, UFR SFA, Université Nangui Abrogoua, Abidjan, Ivory Coast

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

Doumbia Siriki, Dembele Georges Stephane, Tuo Nanou Tieba, Konate Bibata, Kodjo Charles, et al. (2023). Study of the Quantitative Structure Activity Relationship (QSAR) of a Series of Molecules Derived from Thioureas with Anticancer Activities in the Liver. Science Journal of Chemistry, 11(3), 78-87. https://doi.org/10.11648/j.sjc.20231103.12

Copy | Download

ACS Style

Doumbia Siriki; Dembele Georges Stephane; Tuo Nanou Tieba; Konate Bibata; Kodjo Charles, et al. Study of the Quantitative Structure Activity Relationship (QSAR) of a Series of Molecules Derived from Thioureas with Anticancer Activities in the Liver. Sci. J. Chem. 2023, 11(3), 78-87. doi: 10.11648/j.sjc.20231103.12

Copy | Download

AMA Style

Doumbia Siriki, Dembele Georges Stephane, Tuo Nanou Tieba, Konate Bibata, Kodjo Charles, et al. Study of the Quantitative Structure Activity Relationship (QSAR) of a Series of Molecules Derived from Thioureas with Anticancer Activities in the Liver. Sci J Chem. 2023;11(3):78-87. doi: 10.11648/j.sjc.20231103.12

Copy | Download

@article{10.11648/j.sjc.20231103.12,
  author = {Doumbia Siriki and Dembele Georges Stephane and Tuo Nanou Tieba and Konate Bibata and Kodjo Charles and Ziao Nahosse},
  title = {Study of the Quantitative Structure Activity Relationship (QSAR) of a Series of Molecules Derived from Thioureas with Anticancer Activities in the Liver},
  journal = {Science Journal of Chemistry},
  volume = {11},
  number = {3},
  pages = {78-87},
  doi = {10.11648/j.sjc.20231103.12},
  url = {https://doi.org/10.11648/j.sjc.20231103.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.sjc.20231103.12},
  abstract = {The study of the quantitative structure activity relationship (QSAR) of liver cancer was carried out using a series of twenty-five (25) molecules derived from thioureas. The molecular descriptors were obtained after optimization of all these molecules at the B3LYP/6-31+ G (d, p) computational level. The multiple linear regression (MLR) method was used to carry out this study. The use of this method has thus made it possible to obtain a model from the molecular descriptors that are the lipophilicity LogP, the bond lengths d(C=N2) and d(N2-Cphen1), the vibration frequency υ (C =O) and the number of atoms. The results of the statistical indicators obtained from the model (R2=0.906; RMCE=0.198; F= 21.170), allow us to say that this model is acceptable, robust and has good predictive power. Also, the vibration frequency of the carbon-oxygen double bond (C=O), the length of the C-N2 bond and the lipophilicity (LogP) were found to be the priority descriptors in the prediction of the anticancer activity of the liver. Moreover, all the criteria of Tropsha et al. were verified by our model. Moreover, the analysis of the domain of applicability of this model shows that a prediction of the anticancer activity of new derivatives of thiourea is acceptable when its leverage value is less than 1.06, otherwise the anticancer activity of the liver of this compound could not be reliably predicted.},
 year = {2023}
}

Copy | Download

TY  - JOUR
T1  - Study of the Quantitative Structure Activity Relationship (QSAR) of a Series of Molecules Derived from Thioureas with Anticancer Activities in the Liver
AU  - Doumbia Siriki
AU  - Dembele Georges Stephane
AU  - Tuo Nanou Tieba
AU  - Konate Bibata
AU  - Kodjo Charles
AU  - Ziao Nahosse
Y1  - 2023/06/09
PY  - 2023
N1  - https://doi.org/10.11648/j.sjc.20231103.12
DO  - 10.11648/j.sjc.20231103.12
T2  - Science Journal of Chemistry
JF  - Science Journal of Chemistry
JO  - Science Journal of Chemistry
SP  - 78
EP  - 87
PB  - Science Publishing Group
SN  - 2330-099X
UR  - https://doi.org/10.11648/j.sjc.20231103.12
AB  - The study of the quantitative structure activity relationship (QSAR) of liver cancer was carried out using a series of twenty-five (25) molecules derived from thioureas. The molecular descriptors were obtained after optimization of all these molecules at the B3LYP/6-31+ G (d, p) computational level. The multiple linear regression (MLR) method was used to carry out this study. The use of this method has thus made it possible to obtain a model from the molecular descriptors that are the lipophilicity LogP, the bond lengths d(C=N2) and d(N2-Cphen1), the vibration frequency υ (C =O) and the number of atoms. The results of the statistical indicators obtained from the model (R2=0.906; RMCE=0.198; F= 21.170), allow us to say that this model is acceptable, robust and has good predictive power. Also, the vibration frequency of the carbon-oxygen double bond (C=O), the length of the C-N2 bond and the lipophilicity (LogP) were found to be the priority descriptors in the prediction of the anticancer activity of the liver. Moreover, all the criteria of Tropsha et al. were verified by our model. Moreover, the analysis of the domain of applicability of this model shows that a prediction of the anticancer activity of new derivatives of thiourea is acceptable when its leverage value is less than 1.06, otherwise the anticancer activity of the liver of this compound could not be reliably predicted.
VL  - 11
IS  - 3
ER  -

Copy | Download