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Focusing on the moderately active compound (MAC) in the design and development of strategies to optimize the apoptotic effect by molecular mechanics techniques

Yıl 2022, Cilt: 1 Sayı: 3, 118 - 126, 28.02.2023

Asaf Evrim Evren Demokrat Nuha Leyla Yurttaş

https://doi.org/10.55971/EJLS.1209591

Öz

Today, chemotherapeutic agents are mostly used to fight cancer in clinics. But even though they have selectivity for cancer cells, their mechanism of action could result in necrosis. Therefore, we aimed to suggest new design strategies using a moderately active compound (MAC) to get better activity and increase the apoptotic effect in this study. Although MAC, previously synthesized and evaluated for its anticancer properties, has been marked as a moderately active compound, it has let us develop new molecules using its molecular core supported by molecular docking and molecular dynamics simulation. The caspase-3 enzyme was subjected to density functional theory (DFT), docking, and molecular dynamics simulation studies, and the results were analyzed to better understand the structure-activity relationship (SAR); thus, new design strategies were proposed.

Anahtar Kelimeler

Apoptosis DFT molecular dynamics simulation thiazole piperazine

Teşekkür

We are gratefully thankful to Anadolu University and Eskişehir Technical University

Kaynakça

  • Lagorce D, Sperandio O, Galons H, Miteva MA, Villoutreix BO. FAF-Drugs2: free ADME/tox filtering tool to assist drug discovery and chemical biology projects. BMC Bioinformatics. 2008;9:396. https://doi.org/10.1186/1471-2105-9-396
  • Acar Cevik U, Saglik BN, Osmaniye D, et al. Synthesis and docking study of benzimidazole-triazolothiadiazine hybrids as aromatase inhibitors. Arch Pharm (Weinheim). 2020;353(5):e2000008. https://doi.org/10.1002/ardp.202000008
  • Saglik BN, Sen AM, Evren AE, et al. Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors. Z Naturforsch C J Biosci. 2020;75(9-10):353-362. https://doi.org/10.1515/znc-2020-0104
  • Osmaniye D, Karaca Ş, Kurban B, et al. Design, synthesis, molecular docking and molecular dynamics studies of novel triazolothiadiazine derivatives containing furan or thiophene rings as anticancer agents. Bioorg Chem. 2022;122:105709. https://doi.org/10.1016/j.bioorg.2022.105709
  • Dawbaa S, Evren AE, Cantürk Z, Yurttaş L. Synthesis of new thiazole derivatives and evaluation of their antimicrobial and cytotoxic activities. Phosphorus Sulfur Silicon Relat Elem. 2021;196(12):1093-1102. https://doi.org/10.1080/10426507.2021.1972299
  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 1997;23(1-3):3-25. https://doi.org/10.1016/s0169-409x(96)00423-1
  • Wani RR, Chaudhari HK. Docking and 3D QSAR Studies on Substituted Cyclobutylphenyl Quinoline Derivatives as Inhibitors of Bacterial DNA Gyrase. Curr Comput Aided Drug Des. 2018;14(4):322-337. https://doi.org/10.2174/1573409914666180516114700
  • Nuha D, Evren AE, Yılmaz Cankılıç M, Yurttaş L. Design and synthesis of novel 2,4,5-thiazole derivatives as 6-APA mimics and antimicrobial activity evaluation. Phosphorus Sulfur Silicon Relat Elem. 2021;196(10):954-960. https://doi.org/10.1080/10426507.2021.1946537
  • Doak BC, Zheng J, Dobritzsch D, Kihlberg J. How Beyond Rule of 5 Drugs and Clinical Candidates Bind to Their Targets. J Med Chem. 2016;59(6):2312-2327. https://doi.org/10.1021/acs.jmedchem.5b01286
  • Shultz MD. Two Decades under the Influence of the Rule of Five and the Changing Properties of Approved Oral Drugs. J Med Chem. 2019;62(4):1701-1714. https://doi.org/10.1021/acs.jmedchem.8b00686
  • Evren AE, Yurttaş L, Eksellı B, Akalın-Cıftcı G. Novel Tri-substituted Thiazoles Bearing Piperazine Ring: Synthesis and Evaluation of their Anticancer Activity. Lett Drug Des Discov. 2019;16(5):547-555. https://doi.org/10.2174/1570180815666180731122118
  • Frisch M, Trucks G, Schlegel H, et al. Gaussian09, Revision A. Wallingford CT Inc.; 2009. p. 150-166.
  • Dennington R, Keith T, Millam J. GaussView, version 5. 2009.
  • Nuha D, Evren AE, Ciyanci ZS, Temel HE, Akalin Ciftci G, Yurttas L. Synthesis, density functional theory calculation, molecular docking studies, and evaluation of novel 5-nitrothiophene derivatives for anticancer activity. Arch Pharm (Weinheim). 2022;355(9):e2200105. https://doi.org/10.1002/ardp.202200105
  • Nuha D, Evren AE, Kapusiz Ö, et al. Design, synthesis, and antimicrobial activity of novel coumarin derivatives: An in-silico and in-vitro study. J Mol Struct. 2023;1272:134166. https://doi.org/10.1016/j.molstruc.2022.134166
  • Dawbaa S, Nuha D, Evren AE, CankiliÇ MY, YurttaŞ L, Turan G. New Oxadiazole/Triazole Derivatives with Antimicrobial and Antioxidant Properties. J Mol Struct. 2023:135213. https://doi.org/10.1016/j.molstruc.2023.135213
  • Schrödinger Release. 2020-3, Maestro. Schrödinger, LLC, New York, NY, USA; 2020.
  • Yurttaş L, Evren AE, Özkay Y. Synthesis and In Silico Evaluation of Some New 2,4-Disubstituted Thiazole Derivatives. European Journal of Life Sciences. 2022;1(1):8-19. https://doi.org/10.55971/ejls.1089425
  • Evren AE. Bazi yeni kinolin türevlerinin sentezi, antimikrobiyal ve DNA giraz inhibitörü etkilerinin araştırılması [master’s thesis]. Eskişehir, Türkiye: Anadolu Üniversitesi; 2019.
  • Schrödinger Release. 2020-3, LigPrep. Schrödinger, LLC, New York, NY, USA; 2020.
  • Schrödinger Release. 2020-3, Glide. Schrödinger, LLC, New York, NY, USA; 2020.
  • Turan Yucel N, Evren AE, Kandemir U, Can OD. Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study. J Psychopharmacol. 2022;36(7):819-835. https://doi.org/10.1177/02698811221095528
  • Dawbaa S, Evren AE, Saglik BN, Gundogdu-Karaburun N, Karaburun AC. Biological activity evaluation of novel monoamine oxidase inhibitory compounds targeting Parkinson disease. Future Med Chem. 2022;14(22):1663-1679. https://doi.org/10.4155/fmc-2022-0167
  • Evren AE, Nuha D, Dawbaa S, Saglik BN, Yurttas L. Synthesis of novel thiazolyl hydrazone derivatives as potent dual monoamine oxidase-aromatase inhibitors. Eur J Med Chem. 2022;229:114097. https://doi.org/10.1016/j.ejmech.2021.114097
  • Schrödinger Release. 2020-3, Desmond. Schrödinger, LLC, New York, NY, USA; 2020.
  • Fukui K. Role of frontier orbitals in chemical reactions. Science. 1982;218(4574):747-754. https://doi.org/10.1126/science.218.4574.747
  • Politzer P, Murray JS. The fundamental nature and role of the electrostatic potential in atoms and molecules. Theoretical Chemistry Accounts: Theory, Computation, and Modeling (Theoretica Chimica Acta). 2002;108(3):134-142. https://doi.org/10.1007/s00214-002-0363-9
  • Luque FJ, Orozco M, Bhadane PK, Gadre SR. SCRF calculation of the effect of water on the topology of the molecular electrostatic potential. The Journal of Physical Chemistry. 2002;97(37):9380-9384. https://doi.org/10.1021/j100139a021
  • Cade C, Swartz P, MacKenzie SH, Clark AC. Modifying caspase-3 activity by altering allosteric networks. Biochemistry. 2014;53(48):7582-7595. https://doi.org/10.1021/bi500874k
  • Luo M, Lu Z, Sun H, et al. Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity. Cell Res. 2010;20(2):211-222. https://doi.org/10.1038/cr.2010.9

Yıl 2022, Cilt: 1 Sayı: 3, 118 - 126, 28.02.2023

Asaf Evrim Evren Demokrat Nuha Leyla Yurttaş

https://doi.org/10.55971/EJLS.1209591

Öz

Kaynakça

  • Lagorce D, Sperandio O, Galons H, Miteva MA, Villoutreix BO. FAF-Drugs2: free ADME/tox filtering tool to assist drug discovery and chemical biology projects. BMC Bioinformatics. 2008;9:396. https://doi.org/10.1186/1471-2105-9-396
  • Acar Cevik U, Saglik BN, Osmaniye D, et al. Synthesis and docking study of benzimidazole-triazolothiadiazine hybrids as aromatase inhibitors. Arch Pharm (Weinheim). 2020;353(5):e2000008. https://doi.org/10.1002/ardp.202000008
  • Saglik BN, Sen AM, Evren AE, et al. Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors. Z Naturforsch C J Biosci. 2020;75(9-10):353-362. https://doi.org/10.1515/znc-2020-0104
  • Osmaniye D, Karaca Ş, Kurban B, et al. Design, synthesis, molecular docking and molecular dynamics studies of novel triazolothiadiazine derivatives containing furan or thiophene rings as anticancer agents. Bioorg Chem. 2022;122:105709. https://doi.org/10.1016/j.bioorg.2022.105709
  • Dawbaa S, Evren AE, Cantürk Z, Yurttaş L. Synthesis of new thiazole derivatives and evaluation of their antimicrobial and cytotoxic activities. Phosphorus Sulfur Silicon Relat Elem. 2021;196(12):1093-1102. https://doi.org/10.1080/10426507.2021.1972299
  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 1997;23(1-3):3-25. https://doi.org/10.1016/s0169-409x(96)00423-1
  • Wani RR, Chaudhari HK. Docking and 3D QSAR Studies on Substituted Cyclobutylphenyl Quinoline Derivatives as Inhibitors of Bacterial DNA Gyrase. Curr Comput Aided Drug Des. 2018;14(4):322-337. https://doi.org/10.2174/1573409914666180516114700
  • Nuha D, Evren AE, Yılmaz Cankılıç M, Yurttaş L. Design and synthesis of novel 2,4,5-thiazole derivatives as 6-APA mimics and antimicrobial activity evaluation. Phosphorus Sulfur Silicon Relat Elem. 2021;196(10):954-960. https://doi.org/10.1080/10426507.2021.1946537
  • Doak BC, Zheng J, Dobritzsch D, Kihlberg J. How Beyond Rule of 5 Drugs and Clinical Candidates Bind to Their Targets. J Med Chem. 2016;59(6):2312-2327. https://doi.org/10.1021/acs.jmedchem.5b01286
  • Shultz MD. Two Decades under the Influence of the Rule of Five and the Changing Properties of Approved Oral Drugs. J Med Chem. 2019;62(4):1701-1714. https://doi.org/10.1021/acs.jmedchem.8b00686
  • Evren AE, Yurttaş L, Eksellı B, Akalın-Cıftcı G. Novel Tri-substituted Thiazoles Bearing Piperazine Ring: Synthesis and Evaluation of their Anticancer Activity. Lett Drug Des Discov. 2019;16(5):547-555. https://doi.org/10.2174/1570180815666180731122118
  • Frisch M, Trucks G, Schlegel H, et al. Gaussian09, Revision A. Wallingford CT Inc.; 2009. p. 150-166.
  • Dennington R, Keith T, Millam J. GaussView, version 5. 2009.
  • Nuha D, Evren AE, Ciyanci ZS, Temel HE, Akalin Ciftci G, Yurttas L. Synthesis, density functional theory calculation, molecular docking studies, and evaluation of novel 5-nitrothiophene derivatives for anticancer activity. Arch Pharm (Weinheim). 2022;355(9):e2200105. https://doi.org/10.1002/ardp.202200105
  • Nuha D, Evren AE, Kapusiz Ö, et al. Design, synthesis, and antimicrobial activity of novel coumarin derivatives: An in-silico and in-vitro study. J Mol Struct. 2023;1272:134166. https://doi.org/10.1016/j.molstruc.2022.134166
  • Dawbaa S, Nuha D, Evren AE, CankiliÇ MY, YurttaŞ L, Turan G. New Oxadiazole/Triazole Derivatives with Antimicrobial and Antioxidant Properties. J Mol Struct. 2023:135213. https://doi.org/10.1016/j.molstruc.2023.135213
  • Schrödinger Release. 2020-3, Maestro. Schrödinger, LLC, New York, NY, USA; 2020.
  • Yurttaş L, Evren AE, Özkay Y. Synthesis and In Silico Evaluation of Some New 2,4-Disubstituted Thiazole Derivatives. European Journal of Life Sciences. 2022;1(1):8-19. https://doi.org/10.55971/ejls.1089425
  • Evren AE. Bazi yeni kinolin türevlerinin sentezi, antimikrobiyal ve DNA giraz inhibitörü etkilerinin araştırılması [master’s thesis]. Eskişehir, Türkiye: Anadolu Üniversitesi; 2019.
  • Schrödinger Release. 2020-3, LigPrep. Schrödinger, LLC, New York, NY, USA; 2020.
  • Schrödinger Release. 2020-3, Glide. Schrödinger, LLC, New York, NY, USA; 2020.
  • Turan Yucel N, Evren AE, Kandemir U, Can OD. Antidepressant-like effect of tofisopam in mice: A behavioural, molecular docking and MD simulation study. J Psychopharmacol. 2022;36(7):819-835. https://doi.org/10.1177/02698811221095528
  • Dawbaa S, Evren AE, Saglik BN, Gundogdu-Karaburun N, Karaburun AC. Biological activity evaluation of novel monoamine oxidase inhibitory compounds targeting Parkinson disease. Future Med Chem. 2022;14(22):1663-1679. https://doi.org/10.4155/fmc-2022-0167
  • Evren AE, Nuha D, Dawbaa S, Saglik BN, Yurttas L. Synthesis of novel thiazolyl hydrazone derivatives as potent dual monoamine oxidase-aromatase inhibitors. Eur J Med Chem. 2022;229:114097. https://doi.org/10.1016/j.ejmech.2021.114097
  • Schrödinger Release. 2020-3, Desmond. Schrödinger, LLC, New York, NY, USA; 2020.
  • Fukui K. Role of frontier orbitals in chemical reactions. Science. 1982;218(4574):747-754. https://doi.org/10.1126/science.218.4574.747
  • Politzer P, Murray JS. The fundamental nature and role of the electrostatic potential in atoms and molecules. Theoretical Chemistry Accounts: Theory, Computation, and Modeling (Theoretica Chimica Acta). 2002;108(3):134-142. https://doi.org/10.1007/s00214-002-0363-9
  • Luque FJ, Orozco M, Bhadane PK, Gadre SR. SCRF calculation of the effect of water on the topology of the molecular electrostatic potential. The Journal of Physical Chemistry. 2002;97(37):9380-9384. https://doi.org/10.1021/j100139a021
  • Cade C, Swartz P, MacKenzie SH, Clark AC. Modifying caspase-3 activity by altering allosteric networks. Biochemistry. 2014;53(48):7582-7595. https://doi.org/10.1021/bi500874k
  • Luo M, Lu Z, Sun H, et al. Nuclear entry of active caspase-3 is facilitated by its p3-recognition-based specific cleavage activity. Cell Res. 2010;20(2):211-222. https://doi.org/10.1038/cr.2010.9
Toplam 30 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Eczacılık ve İlaç Bilimleri
Bölüm Research Articles
Yazarlar

Asaf Evrim Evren 0000-0002-8651-826X

Demokrat Nuha 0000-0002-7271-6791

Leyla Yurttaş 0000-0002-0957-6044

Yayımlanma Tarihi 28 Şubat 2023
Gönderilme Tarihi 24 Kasım 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 1 Sayı: 3

Kaynak Göster

Vancouver Evren AE, Nuha D, Yurttaş L. Focusing on the moderately active compound (MAC) in the design and development of strategies to optimize the apoptotic effect by molecular mechanics techniques. Eur J Life Sci. 2023;1(3):118-26.
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