Investigation of the Activity of Benzenesulfonamide Derivative Molecules Against Gastric Cancer Proteins with Gaussian Calculations and Docking Analysis

Burak Tüzün

doi:10.17776/csj.1665644

EN

Investigation of the Activity of Benzenesulfonamide Derivative Molecules Against Gastric Cancer Proteins with Gaussian Calculations and Docking Analysis

Abstract

While gastric cancer poses a significant problem in terms of global health with its high mortality rates, the limitations in current treatment methods necessitate the identification of new molecular targets and potential drug candidates. Benzenesulfonamide derivatives are among the compounds that have attracted attention in recent years due to their structural diversity and biological activity potential. In the study, the electronic properties, orbital distributions and thermodynamic stabilities of benzenesulfonamide derivative molecules were calculated using the Gaussian program; thus, the reactivity tendencies of the molecules and their interaction potential with target proteins were tried to be revealed. The calculations were made in the 6-31++g(d,p) basis set at the B3LYP, HF, M062X level. The theoretical data obtained were supported by molecular docking analyses; Docking studies have evaluated the binding affinities and interaction sites of benzenesulfonamide derivatives with the identified gastric cancer proteins, which are PDB ID: 3MAX and 4BKX proteins, in detail. Then, MM-GBSA values were calculated for the molecule with the highest activity among these molecules. Finally, ADME/T calculations were performed to examine the drug potential of the molecules

Keywords

Supporting Institution

This work was supported by the Scientific Research Project Fund of Sivas Cumhuriyet University (CUBAP) under the project number RGD-020.

References

[1] Acar Cevik U., Ünver H., Bostancı H. E., Tüzün B., Gedik N. İ., Kocyigit Ü. M., New hydrazone derivatives: synthesis, characterization, carbonic anhydrase I-II enzyme inhibition, anticancer activity and in silico studies. Zeitschrift für Naturforschung C., (2025) (0) article in press.
[2] Allah A. E. M. A., Mortada S., Tüzün B., Guerrab W., Qostal M., Mague J. T., Ramli Y., Novel Thiohydantoin Derivatives: Design, Synthesis, Spectroscopic Characterization, Crystal Structure, SAR, DFT, Molecular Docking, Pharmacological and Toxicological activities, Journal of Molecular Structure, (2025) 141995.
[3] Karatas H., Kul İ. B., Aydin M., Tüzün B., Taslimi P., Kokbudak Z., Alzheimer’s Disease Drug Design by Synthesis, Characterization, Enzyme Inhibition, In Silico, SAR Analysis and MM-GBSA Analysis of Schiff Bases Derivatives, Korean Journal of Chemical Engineering, (2025) 1-19.
[4] Şahin İ., Çeşme M., Güngör Ö., Özgeriş F. B., Köse M., Tümer, New sulfonamide derivatives based on 1, 2, 3-triazoles: synthesis, in vitro biological activities and in silico studies, Journal of Biomolecular Structure and Dynamics, 42(9) (2024) 4782-4799.
[5] Becke A.D., Density‐functional thermochemistry. I. The effect of the exchange‐only gradient correction, The Journal of Chemical Physics, 96(3) (1992) 2155-2160.
[6] Vautherin D., Brink D. T., Hartree-Fock calculations with Skyrme's interaction. I. Spherical nuclei, Physical Review C, 5(3) (1972) 626.
[7] Hohenstein E. G., Chill S. T., Sherrill C. D., Assessment of the performance of the M05− 2X and M06− 2X exchange-correlation functionals for noncovalent interactions in biomolecules, Journal of Chemical Theory and Computation, 4(12) (2008) 1996-2000.
[8] Bressi, J. C., Jennings, A. J., Skene, R., Wu, Y., Melkus, R., De Jong, R., ... & Gangloff, A. R. Exploration of the HDAC2 foot pocket: Synthesis and SAR of substituted N-(2-aminophenyl) benzamides, Bioorganic & Medicinal Chemistry Letters, 20(10) (2010) 3142-3145.

[9] Millard C. J., Watson P. J., Celardo I., Gordiyenko Y., Cowley S. M., Robinson C. V., Schwabe J. W., Class I HDACs share a common mechanism of regulation by inositol phosphates, Molecular Cell, 51(1) (2013) 57-67.
[10] Dennington R., Keith T. A., Millam J. M., GaussView 6.0. 16. Semichem Inc.: Shawnee Mission, KS, (2016) USA.
[11] 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 M., Toyota K., Fukuda R., Hasegawa J., Ishida M., Nakajima T., Honda Y., Kitao O., Nakai H., Vreven T., Montgomery J.A., Peralta J.E., Ogliaro F., Bearpark M., Heyd J.J., Brothers E., Kudin K.N., Staroverov V.N., Kobayashi R., Normand J., Raghavachari K., Rendell A., Burant J.C., Iyengar S.S., Tomasi J., Cossi M., Rega N., Millam J.M., Klene M., Knox J.E., Cross J.B., Bakken V., Adamo C., Jaramillo J., Gomperts R., Stratmann R.E., Yazyev O., Austin A.J., Cammi R., Pomelli C., Ochterski J.W., Martin R.L., Morokuma K., Zakrzewski V.G., Voth G.A., Salvador P., Dannenberg J.J., Dapprich S., Daniels A.D., Farkas O., Foresman J.B., Ortiz J.V., Cioslowski J.,Fox D.J. (2009) Gaussian 09, revision D.01. Gaussian Inc, Wallingford CT
[12] Medetalibeyoğlu H., Atalay A., Sağlamtaş R., Manap S., Ortaakarsu A. B., Ekinci E., Tüzün B., Synthesis, design, and cholinesterase inhibitory activity of novel 1, 2, 4-triazole Schiff bases: A combined experimental and computational approach, International Journal of Biological Macromolecules, 306 (2025) 141350.
[13] Akkus M., Kirici M., Poustforoosh A., Erdogan M. K., Gundogdu R., Tüzün B., Taslimi P., Phenolic Compounds: Investigating Their Anti-Carbonic Anhydrase, Anti-Cholinesterase, Anticancer, Anticholinergic, and Antiepileptic Properties Through Molecular Docking, MM-GBSA, and Dynamics Analyses, Korean Journal of Chemical Engineering, (2025) 1-20.
[14] Schrödinger Release 2022-4: Maestro, Schrödinger, LLC, New York, NY, 2022.
[15] Schrödinger Release 2022-4: Protein Preparation Wizard; Epik, Schrödinger, LLC, New York, NY, 2022; Impact, Schrödinger, LLC, New York, NY; Prime, Schrödinger, LLC, New York, NY, 2022
[16] Schrödinger Release 2022-4: LigPrep, Schrödinger, LLC, New York, NY, 2022.
[17] Shahzadi I., Zahoor A. F., Tüzün B., Mansha A., Anjum M. N., Rasul A., Mojzych M., Repositioning of acefylline as anti-cancer drug: Synthesis, anticancer and computational studies of azomethines derived from acefylline tethered 4-amino-3-mercapto-1, 2, 4-triazole, Plos One, 17(12) (2022) e0278027.
[18] El Faydy M., Lakhrissi L., Dahaieh N., Ounine K., Tüzün B., Chahboun N., Zarrouk A. Synthesis, Biological Properties, and Molecular Docking Study of Novel 1, 2, 3-Triazole-8-quinolinol Hybrids, ACS omega, 9(23) (2024) 25395–25409.
[19] Schrödinger Release 2022-4: QikProp, Schrödinger, LLC, New York, NY, 2022.
[20] Ullah N., Alam A., Tüzün B., Rehman N. U., Ayaz M., Elhenawy A. A., Ahmad M., Synthesis of novel thiazole derivatives containing 3-methylthiophene carbaldehyde as potent anti α-glucosidase agents: In vitro evaluation, molecular docking, dynamics, MM-GBSA, and DFT studies. Journal of Molecular Structure, 1321 (2025) 140070.
[21] Yalazan H., Koç D., Aydın Kose F., Fandaklı S., Tüzün B., Akgül, M. İ, Kantekin H. Design, syntheses, theoretical calculations, MM-GBSA, potential anti-cancer and enzyme activities of novel Schiff base compounds, Journal of Biomolecular Structure and Dynamics, 42(23) (2024) 13100-13113.
[22] Manap S., Medetalibeyoğlu H., Kılıç A., Karataş O. F., Tüzün B., Alkan M., Yüksek H., Synthesis, molecular modeling investigation, molecular dynamic and ADME prediction of some novel Mannich bases derived from 1, 2, 4-triazole, and assessment of their anticancer activity, Journal of Biomolecular Structure and Dynamics, 42(21) (2024) 11916-11930.
[23] Rafik A., Tuzun B., Zouihri H., Poustforoosh A., Hsissou R., Elhenaey A. A., Guedira T., Morphology studies, optic proprieties, hirschfeld electrostatic potential mapping, docking molecular anti-inflammatory, and dynamic molecular approaches of hybrid phosphate, Journal of the Indian Chemical Society, 101(11) (2024) 101419.
[24] Barghady N., Assou S. A., Er-Rajy M., Boujdi K., Arzine A., Rhazi Y., El Yazidi M., Design, synthesis, characterization, and theoretical calculations, along with in silico and in vitro antimicrobial proprieties of new isoxazole-amide conjugates, Open Chemistry, 22(1) (2024) 20240109.
[25] Schrader T., Khanifaev J., Perlt E., Koopmans' theorem for acidic protons, Chemical Communications, 59(93) (2023) 13839-13842.
[26] Phillips J. C., Generalized Koopmans' Theorem., Physical Review, 123(2) (1961) 420.
[27] Pearson R. G., Hard and soft acids and bases, Journal of the American Chemical Society, 85(22) (1963) 3533-3539.
[28] Pearson R. G., Hard and soft acids and bases, Journal Of The American Chemical Society, 85(22) (1963) 3533-3539.
[29] Ayers P. W., An elementary derivation of the hard/soft-acid/base principle, The Journal of Chemical Physics, 122(14) (2005).
[30] Parr R. G., Chattaraj P. K., Principle of Maximum Hardness, Journal of the American Chemical Society, 113(5) (1991) 1854-1855.
[31] Goswami A. K., Aboul-Soud M. A., Gogoi N., El-Shazly M., Giesy J. P., Tüzün B., Sharma H. K., Integrative in silico evaluation of the antiviral potential of terpenoids and its metal complexes derived from Homalomena aromatica based on main protease of SARS-CoV-2, Open Chemistry, 22(1) (2024) 20240085.
[32] Medetalibeyoğlu H., Manap S., Alkan M., Beytur M., Barlak N., Karatas O. F., Taslimi P., Novel Schiff Bases: Synthesis, characterization, bioactivity, cytotoxicity, and computational evaluations, Polycyclic Aromatic Compounds, (2024) 1-19.
[33] Tapera M., Kekeçmuhammed H., Tüzün B., Daştan S. D., Çelik M. S., Taslimi P., Sarıpınar E., Novel 1, 2, 4-triazole-maleamic acid derivatives: Synthesis and evaluation as anticancer agents with carbonic anhydrase inhibitory activity, Journal of Molecular Structure, 1313 (2024) 138680.
[34] Alishba Ali I., Hameed S., Khan K. M., Salar U., Taha M., Ulukaya E., Exploring Benzo [b][1, 4] Thiazine Derivatives: Multitarget Inhibition, Structure–Activity Relationship, Molecular Docking, and ADMET Analysis, ChemistrySelect, 9(38) (2024) e202404087.
[35] Belkheiri A., Dahmani K., Mzioud K., Rbaa M., Galai M., Hmada A., Al-Maswar, B. M., Advanced evaluation of novel quinoline derivatives for corrosion inhibition of mild steel in acidic environments: A comprehensive electrochemical, computational, and surface study, International Journal of Electrochemical Science, 19(10) (2024) 100772.
[36] Çelik M. S., Kütük N., Yenidünya A. F., Çetinkaya S., Tüzün B., Removal of safranin O from wastewater using Streptomyces griseobrunneus dead biomass and in silico calculations, Biomass Conversion and Biorefinery, 14(20) (2024) 25873-25884.
[37] Zahirović A., Fočak M., Fetahović S., Tüzün B., Višnjevac A., Muzika V., Roca S., Hydrazone-flavonol based oxidovanadium (V) complexes: Synthesis, characterization and antihyperglycemic activity of chloro derivative in vivo, Journal of Inorganic Biochemistry, 258 (2024) 112637.
[38] Lipinski C. A., Lead-and drug-like compounds: the rule-of-five revolution, Drug Discovery Today: Technologies, 1(4) (2004) 337-341.
[39] Lipinski C. A., Lombardo F., Dominy B. W., Feeney P. J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Advanced Drug Delivery Reviews, 23 (1997) 3-25.
[40] Jorgensen W.J., Duffy E.M., Prediction of drug solubility from structure, Advanced Drug Delivery Reviews, 54(3) (2002) 355-366.

Details

Primary Language

English

Subjects

Physical Organic Chemistry

Journal Section

Research Article

Authors

Burak Tüzün ^*
0000-0002-0420-2043
Türkiye

Publication Date

June 30, 2025

Submission Date

March 26, 2025

Acceptance Date

May 21, 2025

Published in Issue

Year 2025 Volume: 46 Number: 2

DOI

https://doi.org/10.17776/csj.1665644

IZ

https://izlik.org/JA45YC32GW

Cite

RIS / Bibtex

APA

Tüzün, B. (2025). Investigation of the Activity of Benzenesulfonamide Derivative Molecules Against Gastric Cancer Proteins with Gaussian Calculations and Docking Analysis. Cumhuriyet Science Journal, 46(2), 338-347. https://doi.org/10.17776/csj.1665644

Cited By

Multifunctional nickel (II) phthalocyanines with oxygen-bridged substituents: Synthesis, biological evaluation, and computational studies

Journal of Molecular Structure

https://doi.org/10.1016/j.molstruc.2025.145104

Öz

Investigation of the Activity of Benzenesulfonamide Derivative Molecules Against Gastric Cancer Proteins with Gaussian Calculations and Docking Analysis

Abstract

Keywords

Supporting Institution

References

Details

Primary Language

Subjects

Journal Section

Authors

Publication Date

Submission Date

Acceptance Date

Published in Issue

DOI

IZ

Cite

Cited By

Multifunctional nickel (II) phthalocyanines with oxygen-bridged substituents: Synthesis, biological evaluation, and computational studies