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Investigation of Dimethylcyclopentane Derivatives as Potential Drug Candidates for Thyroid Disorders Using Computational Chemistry Methods

Yıl 2025, Cilt: 9 Sayı: 5, 86 - 95

Süeda Kıska

Öz

In this study, the potential use of dimethylcyclopentane (DMCP) derivatives as active agents for the treatment of thyroid disorders was evaluated through computational chemistry approaches. The primary objective of the study was to investigate the interaction potential of DMCP-based compounds with transthyretin (TTR) and thyroid hormone receptors (THR), which play key roles in the transport and regulation of thyroid hormones. To this end, various DMCP derivatives with different configurations were designed, and their geometries and electronic properties were determined using Density Functional Theory (DFT) optimizations. Subsequently, molecular docking studies were conducted using human transthyretin (PDB ID: 2ROX) and thyroid hormone receptor (PDB ID: 1NAV) as the target proteins. The docking analyses revealed that certain DMCP derivatives exhibited strong binding affinities toward the thyroid receptor and formed stable interactions at critical binding sites. Furthermore, the drug-like properties of these compounds were assessed through ADME/Tox analysis, and candidates with favorable bioavailability profiles were identified. The results indicate that specific dimethylcyclopentane derivatives may serve as promising drug candidates capable of contributing to the regulation of thyroid hormones through interaction with the thyroid receptor.

Anahtar Kelimeler

Dimethylcyclopentane Thyroid DFT Docking

Kaynakça

  • [1] Y. Sekijima, R. L. Wiseman, J. Matteson, P. Hammarström, S. R. Miller, A. R. Sawkar, ... J. W. Kelly, The biological and chemical basis for tissue-selective amyloid disease. Cell, 121(1) (2005) 73-85.
  • [2] F. Flamant, S. Y. Cheng, A. N. Hollenberg, L. C. Moeller, J. Samarut, F. E. Wondisford, ... S. Refetoff, Thyroid hormone signaling pathways: time for a more precise nomenclature. Endocrinology, 158(7) (2017) 2052-2057.
  • [3] G. Sliwoski, S. Kothiwale, J. Meiler, E. W. Lowe Jr, Computational methods in drug discovery. Pharmacological reviews, 66(1) (2014) 334-395.
  • [4] E. Lionta, G. Spyrou, K. D. Vassilatis, Z. Cournia, Structure-based virtual screening for drug discovery: principles, applications and recent advances. Current Topics in Medicinal Chemistry, 14(16) (2014) 1923–1938.
  • [5] Wang, Y. et al. (2021). Exploration of cyclopentane-based scaffolds in medicinal chemistry: Current progress and future perspectives. European Journal of Medicinal Chemistry, 224, 113707.
  • [6] B. S. Desai, N. S. Kumar, M. Singh, Cyclic moieties in modern drug design: Applications and structural advantages. Bioorganic Chemistry, 139 (2023) 106661.
  • [7] Z. Zhao, L. Xie, L. Xie, P. E. Bourne, Structure and function of bioactive cyclopentane derivatives in drug discovery. Expert Opinion on Drug Discovery, 17(4) (2022) 399–412.
  • [8] F. Jensen, Introduction to computational chemistry. John wiley & sons (2017).
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  • [11] P. K. Chattaraj, D. R. Roy, P. W. Ayers, Chemical reactivity descriptors: Recent advances. Chemical Reviews, 120(19), (2020) 9443–9483.
  • [12] E. Harder, W. Damm, J. R. Maple, C. Wu, M. Reboul, J. Y. Xiang, ... W. Sherman, OPLS3: A force field providing broad coverage of drug-like small molecules and proteins. Journal of Chemical Theory and Computation, 12(1) (2016) 281–296.
  • [13] Schrödinger Release 2022-4: LigPrep. Schrödinger, LLC, New York, NY, (2022).
  • [14] R. A. Friesner, R. B. Murphy, M. P. Repasky, J. R. Greenwood, T. A. Halgren, J. C. Shelley, Extra precision Glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein–ligand complexes. Journal of Medicinal Chemistry, 64(9) (2021) 4191–4200.
  • [15] Schrödinger Release 2022-4: QikProp. Schrödinger, LLC, New York, NY, (2022).
  • [16] F. D. Prieto-Martínez, E. López-López, J. L. Medina-Franco, J. J. Naveja, Applications of QikProp in early-stage drug discovery: A comprehensive overview. Drug Discovery Today, 27(3) (2022) 823–830.
  • [17] B. Natarajan, V. Veeramani, S. Periandy, DFT-based electronic structure and molecular docking analysis of bioactive benzofuran derivatives. Journal of Molecular Structure, 1221 (2020) 128743.
  • [18] M. T. Islam, M. M. Hasan, M. T. Hossain, (2021). Quantum chemical insights into drug-like molecules: HOMO-LUMO, NBO, and molecular docking analyses. Heliyon, 7(4) (2021) e06730.
  • [19] M. Rahaman, M. K. Hossain, F. Ahmed, In silico design and DFT-based reactivity study of potential anticancer compounds derived from cyclic scaffolds. Computational Biology and Chemistry, 102 (2023) 107799.
  • [20] S. Kozuch, S. M. Bachrach, J. M. Martin, Molecular electrostatic potential as a descriptor for noncovalent interactions. Chemical Society Reviews, 49(15) (2020) 5251–5266.
  • [21] Z. Miao, Y. Liu, J. Gao, Visualization of electrostatic potential surfaces and their applications in molecular interactions. Frontiers in Chemistry, 9 (2021) 684729.
  • [22] R. A. Friesner, J. L. Banks, R. B. Murphy, T. A. Halgren, J. J. Klicic, D. T. Mainz, ... M. Shelley, Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. Journal of Medicinal Chemistry, 47(7) (2004) 1739–1749.
  • [23] A. L. Hopkins, C. R. Groom, A. Alex, Ligand efficiency: A useful metric for lead selection. Drug Discovery Today, 9(10) (2004) 430–431.
  • [24] T. A. Halgren, R. B. Murphy, R. A. Friesner, H. S. Beard, L. L. Frye, W. T. Pollard, J. L. Banks, Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. Journal of Medicinal Chemistry, 47(7) (2004)1750–1759.
  • [25] J. Muthu Mohamed, S. Manoharan, B. Senthil Kumar, P. Parthiban, Molecular docking analysis of potential phytochemicals against SARS-CoV-2 main protease and spike glycoprotein. Computational Biology and Chemistry, 95 (2021) 107597.
  • [26] S. Kömücüoğlu, G. Demir, M. Şahin, QSAR and ADME evaluation of cyclopentane derivatives via QikProp. Journal of Computational Chemistry, 43(4) (2022) 319–330.
  • [27] P. Taslimi, B. M. Razavi, H. Hosseinzadeh, In silico ADME/T analysis of chalcone derivatives using QikProp. Drug Design, Development and Therapy, 14 (2020) 3603–3619.
  • [28] S. Desmukh, M. Patil, B. Ghosh, hERG liability assessment of novel small molecules using computational models. European Journal of Medicinal Chemistry, 260 (2023) 115996.
  • [29] B. Kantarci, S. Öztürk, Ö. Kaya, Lipophilicity and dipole moment correlation in QikProp predictions. Journal of Molecular Modeling, 27 (2021) 65.

Yıl 2025, Cilt: 9 Sayı: 5, 86 - 95

Süeda Kıska

Öz

Kaynakça

  • [1] Y. Sekijima, R. L. Wiseman, J. Matteson, P. Hammarström, S. R. Miller, A. R. Sawkar, ... J. W. Kelly, The biological and chemical basis for tissue-selective amyloid disease. Cell, 121(1) (2005) 73-85.
  • [2] F. Flamant, S. Y. Cheng, A. N. Hollenberg, L. C. Moeller, J. Samarut, F. E. Wondisford, ... S. Refetoff, Thyroid hormone signaling pathways: time for a more precise nomenclature. Endocrinology, 158(7) (2017) 2052-2057.
  • [3] G. Sliwoski, S. Kothiwale, J. Meiler, E. W. Lowe Jr, Computational methods in drug discovery. Pharmacological reviews, 66(1) (2014) 334-395.
  • [4] E. Lionta, G. Spyrou, K. D. Vassilatis, Z. Cournia, Structure-based virtual screening for drug discovery: principles, applications and recent advances. Current Topics in Medicinal Chemistry, 14(16) (2014) 1923–1938.
  • [5] Wang, Y. et al. (2021). Exploration of cyclopentane-based scaffolds in medicinal chemistry: Current progress and future perspectives. European Journal of Medicinal Chemistry, 224, 113707.
  • [6] B. S. Desai, N. S. Kumar, M. Singh, Cyclic moieties in modern drug design: Applications and structural advantages. Bioorganic Chemistry, 139 (2023) 106661.
  • [7] Z. Zhao, L. Xie, L. Xie, P. E. Bourne, Structure and function of bioactive cyclopentane derivatives in drug discovery. Expert Opinion on Drug Discovery, 17(4) (2022) 399–412.
  • [8] F. Jensen, Introduction to computational chemistry. John wiley & sons (2017).
  • [9] Schrödinger Release 2022-4: Maestro. Schrödinger, LLC, New York, NY, (2022).
  • [10] M. E. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. Robb, J. R. Cheeseman, ... D. J. Fox, Gaussian 16 (2016).
  • [11] P. K. Chattaraj, D. R. Roy, P. W. Ayers, Chemical reactivity descriptors: Recent advances. Chemical Reviews, 120(19), (2020) 9443–9483.
  • [12] E. Harder, W. Damm, J. R. Maple, C. Wu, M. Reboul, J. Y. Xiang, ... W. Sherman, OPLS3: A force field providing broad coverage of drug-like small molecules and proteins. Journal of Chemical Theory and Computation, 12(1) (2016) 281–296.
  • [13] Schrödinger Release 2022-4: LigPrep. Schrödinger, LLC, New York, NY, (2022).
  • [14] R. A. Friesner, R. B. Murphy, M. P. Repasky, J. R. Greenwood, T. A. Halgren, J. C. Shelley, Extra precision Glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein–ligand complexes. Journal of Medicinal Chemistry, 64(9) (2021) 4191–4200.
  • [15] Schrödinger Release 2022-4: QikProp. Schrödinger, LLC, New York, NY, (2022).
  • [16] F. D. Prieto-Martínez, E. López-López, J. L. Medina-Franco, J. J. Naveja, Applications of QikProp in early-stage drug discovery: A comprehensive overview. Drug Discovery Today, 27(3) (2022) 823–830.
  • [17] B. Natarajan, V. Veeramani, S. Periandy, DFT-based electronic structure and molecular docking analysis of bioactive benzofuran derivatives. Journal of Molecular Structure, 1221 (2020) 128743.
  • [18] M. T. Islam, M. M. Hasan, M. T. Hossain, (2021). Quantum chemical insights into drug-like molecules: HOMO-LUMO, NBO, and molecular docking analyses. Heliyon, 7(4) (2021) e06730.
  • [19] M. Rahaman, M. K. Hossain, F. Ahmed, In silico design and DFT-based reactivity study of potential anticancer compounds derived from cyclic scaffolds. Computational Biology and Chemistry, 102 (2023) 107799.
  • [20] S. Kozuch, S. M. Bachrach, J. M. Martin, Molecular electrostatic potential as a descriptor for noncovalent interactions. Chemical Society Reviews, 49(15) (2020) 5251–5266.
  • [21] Z. Miao, Y. Liu, J. Gao, Visualization of electrostatic potential surfaces and their applications in molecular interactions. Frontiers in Chemistry, 9 (2021) 684729.
  • [22] R. A. Friesner, J. L. Banks, R. B. Murphy, T. A. Halgren, J. J. Klicic, D. T. Mainz, ... M. Shelley, Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. Journal of Medicinal Chemistry, 47(7) (2004) 1739–1749.
  • [23] A. L. Hopkins, C. R. Groom, A. Alex, Ligand efficiency: A useful metric for lead selection. Drug Discovery Today, 9(10) (2004) 430–431.
  • [24] T. A. Halgren, R. B. Murphy, R. A. Friesner, H. S. Beard, L. L. Frye, W. T. Pollard, J. L. Banks, Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. Journal of Medicinal Chemistry, 47(7) (2004)1750–1759.
  • [25] J. Muthu Mohamed, S. Manoharan, B. Senthil Kumar, P. Parthiban, Molecular docking analysis of potential phytochemicals against SARS-CoV-2 main protease and spike glycoprotein. Computational Biology and Chemistry, 95 (2021) 107597.
  • [26] S. Kömücüoğlu, G. Demir, M. Şahin, QSAR and ADME evaluation of cyclopentane derivatives via QikProp. Journal of Computational Chemistry, 43(4) (2022) 319–330.
  • [27] P. Taslimi, B. M. Razavi, H. Hosseinzadeh, In silico ADME/T analysis of chalcone derivatives using QikProp. Drug Design, Development and Therapy, 14 (2020) 3603–3619.
  • [28] S. Desmukh, M. Patil, B. Ghosh, hERG liability assessment of novel small molecules using computational models. European Journal of Medicinal Chemistry, 260 (2023) 115996.
  • [29] B. Kantarci, S. Öztürk, Ö. Kaya, Lipophilicity and dipole moment correlation in QikProp predictions. Journal of Molecular Modeling, 27 (2021) 65.
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Moleküler Görüntüleme
Bölüm Research Article
Yazarlar

Süeda Kıska 0009-0001-3523-1154

Erken Görünüm Tarihi 2 Temmuz 2025
Yayımlanma Tarihi
Gönderilme Tarihi 12 Haziran 2025
Kabul Tarihi 24 Haziran 2025
Yayımlandığı Sayı Yıl 2025 Cilt: 9 Sayı: 5

Kaynak Göster

APA Kıska, S. (2025). Investigation of Dimethylcyclopentane Derivatives as Potential Drug Candidates for Thyroid Disorders Using Computational Chemistry Methods. Turkish Computational and Theoretical Chemistry, 9(5), 86-95.
AMA Kıska S. Investigation of Dimethylcyclopentane Derivatives as Potential Drug Candidates for Thyroid Disorders Using Computational Chemistry Methods. Turkish Comp Theo Chem (TC&TC). Temmuz 2025;9(5):86-95.
Chicago Kıska, Süeda. “Investigation of Dimethylcyclopentane Derivatives As Potential Drug Candidates for Thyroid Disorders Using Computational Chemistry Methods”. Turkish Computational and Theoretical Chemistry 9, sy. 5 (Temmuz 2025): 86-95.
EndNote Kıska S (01 Temmuz 2025) Investigation of Dimethylcyclopentane Derivatives as Potential Drug Candidates for Thyroid Disorders Using Computational Chemistry Methods. Turkish Computational and Theoretical Chemistry 9 5 86–95.
IEEE S. Kıska, “Investigation of Dimethylcyclopentane Derivatives as Potential Drug Candidates for Thyroid Disorders Using Computational Chemistry Methods”, Turkish Comp Theo Chem (TC&TC), c. 9, sy. 5, ss. 86–95, 2025.
ISNAD Kıska, Süeda. “Investigation of Dimethylcyclopentane Derivatives As Potential Drug Candidates for Thyroid Disorders Using Computational Chemistry Methods”. Turkish Computational and Theoretical Chemistry 9/5 (Temmuz 2025), 86-95.
JAMA Kıska S. Investigation of Dimethylcyclopentane Derivatives as Potential Drug Candidates for Thyroid Disorders Using Computational Chemistry Methods. Turkish Comp Theo Chem (TC&TC). 2025;9:86–95.
MLA Kıska, Süeda. “Investigation of Dimethylcyclopentane Derivatives As Potential Drug Candidates for Thyroid Disorders Using Computational Chemistry Methods”. Turkish Computational and Theoretical Chemistry, c. 9, sy. 5, 2025, ss. 86-95.
Vancouver Kıska S. Investigation of Dimethylcyclopentane Derivatives as Potential Drug Candidates for Thyroid Disorders Using Computational Chemistry Methods. Turkish Comp Theo Chem (TC&TC). 2025;9(5):86-95.

Journal Full Title: Turkish Computational and Theoretical Chemistry


Journal Abbreviated Title: Turkish Comp Theo Chem (TC&TC)