شیمى کاربردى روز

شیمى کاربردى روز

سنتز و شناسایی ترکیبات باز شیف با پتانسیل درمانی بالا در سرطان و مقابله با ویروس‌های کرونا بر پایه روش داکینگ مولکولی

نوع مقاله : مقاله علمی پژوهشی

نویسندگان
1 دانشکده شیمی، دانشگاه سمنان، سمنان، ایران
2 دانشکده شیمی، دانشگاه لهستان
چکیده
در دهه‌های اخیر، سرطان به دومین عامل مرگ‌ومیر در جهان تبدیل شده و مقاومت آن در برابر درمان‌های متداول مانند شیمی‌درمانی، چالش‌های زیادی ایجاد کرده‌است. از جمله اهداف مهم در درمان سرطان، پروتئین BCL-2(4LXD) است که نقش کلیدی در جلوگیری از آپوپتوز و بقای سلول‌های سرطانی دارد. از سوی دیگر، ویروس کرونا نیز به یکی از بحران‌های بزرگ قرن ۲۱ تبدیل شده است. در این راستا، طراحی ترکیبات باز شیف که توانایی برهم‌کنش با فلزات واسطه و مهار پروتئین‌های هدف را داشته، اهمیت زیادی در داروسازی و بیوتکنولوژی پیدا کرده‌است. در این پژوهش، یک لیگاند باز شیف جدید بر پایه ۲و۵-دی‌هیدروکسی‌بنزآلدهید و ۲-آمینوبنزیل‌الکل و همچنین کمپلکس نیکل (II) آن سنتز و شناسایی شدند. بررسی داکینگ مولکولی نشان داد که این ترکیبات توانایی قابل‌توجهی در مهار پروتئین ویروس کرونا (6Y2F) و پروتئین سرطان BCL-2(4LXD) دارند.برای ارزیابی توان اتصال ترکیبات باز شیف، مقایسه انرژی کل آن‌ها با دو ترکیب مرجع یعنی کریزوتینیب (داروی ضد سرطان ) کلروکین (داروی ضدویروس) انجام شد. مقادیر منفی انرژی‌های اتصال نشان‌دهنده پایداری مناسب این ترکیبات با پروتئین بوده وآن‌ها را به عنوان گزینه‌هایی با پتانسیل درمانی برای سرطان و کووید-۱۹ مطرح می‌سازند.
کلیدواژه‌ها
موضوعات

عنوان مقاله English

Synthesis and Characterization of Schiff Base Compounds with High Therapeutic Potential Against Cancer and Coronaviruses Based on Molecular Docking Method

نویسندگان English

Melika Rabiee 1
Mehdi Salehi 1
Maciej Kubicki 2
1 Department of Chemistry, Semnan University, Semnan, Iran
2 Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznansiego 8, 61-614 Poznan, Poland
چکیده English

In recent decades, cancer has become the second leading cause of death worldwide, with its resistance to conventional treatments such as chemotherapy posing significant challenges. One of the key therapeutic targets in cancer treatment is the BCL-2(4LXD) protein, which plays a crucial role in inhibiting apoptosis and promoting cancer cell survival. Meanwhile, the coronavirus has emerged as a major global crisis in the 21st century. In this context, the design of Schiff base compounds, which can coordinate with transition metals and inhibit target proteins, has gained considerable importance in pharmaceutical and biotechnological research. In this study, a novel Schiff base ligand derived from 2,5-dihydroxybenzaldehyde and 2-aminobenzyl alcohol, along with its Nickel(II) complex, was synthesized and characterized. Molecular docking analysis revealed that these compounds exhibit significant inhibitory potential against the coronavirus main protease (PDB ID: 6Y2F) and the cancer-related BCL-2 protein (PDB ID: 4LXD). The negative binding energies indicate favorable and stable interactions between the compounds and the target proteins. To evaluate the binding potential of the synthesized Schiff base compounds, their total energy values were compared with those of two reference drugs: Crizotinib (an anticancer agent) and Chloroquine (an antiviral agent). These results suggest that both the free ligand and its Nickel(II) complex may serve as promising therapeutic candidates for the treatment of cancer and COVID-19.

کلیدواژه‌ها English

Schiff base
Cancer
Coronavirus
Complex
Molecular docking
[1] Moss, G. P., Smith, P. A. S., & Tavernier, D. (1995). Glossary of class names of organic compounds and reactivity intermediates based on structure (IUPAC Recommendations 1995). Pure and applied chemistry67(8-9), 1307-1375.
[2] Parvarinezhad, S., & Salehi, M. (2021). Synthesis, characterization, anti-proliferative activity and chemistry computation of DFT theoretical methods of hydrazine-based Schiff bases derived from methyl acetoacetate and α-hydroxyacetophenone. Journal of Molecular Structure1225, 129086.
[3] Mahmoud, W. H., Deghadi, R. G., & Mohamed, G. G. (2016). Novel Schiff base ligand and its metal complexes with some transition elements. Synthesis, spectroscopic, thermal analysis, antimicrobial and in vitro anticancer activity. Applied Organometallic Chemistry30(4), 221-230.
[4] Lundgren, R. J., & Stradiotto, M. (2016). Key concepts in ligand design: an introduction. Ligand Design in Metal Chemistry: Reactivity and Catalysis, 1-14.
[5] Kumar, B., Devi, J., & Manuja, A. (2023). Synthesis, structure elucidation, antioxidant, antimicrobial, anti-inflammatory and molecular docking studies of transition metal (II) complexes derived from heterocyclic Schiff base ligands. Research on Chemical Intermediates49(6), 2455-2493.
[6] Devi, J., Kumar, S., Kumar, B., Asija, S., & Kumar, A. (2022). Synthesis, structural analysis, in vitro antioxidant, antimicrobial activity and molecular docking studies of transition metal complexes derived from Schiff base ligands of 4-(benzyloxy)-2-hydroxybenzaldehyde. Research on Chemical Intermediates48(4), 1541-1576.
[7] Pellei, M., Del Bello, F., Porchia, M., & Santini, C. (2021). Zinc coordination complexes as anticancer agents. Coordination Chemistry Reviews445, 214088.
[8] Neelakantan, M. A., Esakkiammal, M., Mariappan, S. S., Dharmaraja, J., & Jeyakumar, T. (2010). Synthesis, characterization and biocidal activities of some schiff base metal complexes. Indian Journal of Pharmaceutical Sciences72(2), 216.
[9] Devi, J., Sharma, S., Kumar, S., Kumar, B., Kumar, D., Jindal, D. K., & Das, S. (2022). Synthesis, characterization, in vitro antimicrobial and cytotoxic studies of Co (II), Ni (II), Cu (II), and Zn (II) complexes obtained from Schiff base ligands of 1, 2, 3, 4‐tetrahydro‐naphthalen‐1‐ylamine. Applied Organometallic Chemistry36(8), e6760.
[10] Kursunlu, A. N., Guler, E., Sevgi, F., & Ozkalp, B. (2013). Synthesis, spectroscopic characterization and antimicrobial studies of Co (II), Ni (II), Cu (II) and Zn (II) complexes with Schiff bases derived from 5-bromo-salicylaldehyde. Journal of Molecular Structure1048, 476-481.
[11] Behzad, M., Ghasemi, L., & Abbasi, A. (2025). Crystal structural characterization, molecular docking and ADMET analysis of new Cu (II) Schiff base complexes: Antiviral properties against SARS-CoV-2 and HPV. Polyhedron, 117549.
[12] Kumar, S., & Choudhary, M. (2023). New nickel (II) Schiff base complexes as potential tools against SARS-CoV-2 Omicron target proteins: an in silico approach. New Journal of Chemistry47(5), 2350-2371.
[13] Musib, D., Pal, M., Allam, U. S., & Roy, M. (2022). Brief History, Pathophysiology, Transmission of SARS-CoV-2 Virus, and Recent Advances on Transition Metal Complexes and Nanocomposites as the Potent Antiviral Agents from COVID-19 Perspectives. Nanostructured Biomaterials: Basic Structures and Applications, 1-48.
[14] Chhetri, A., Chettri, S., Rai, P., Mishra, D. K., Sinha, B., & Brahman, D. (2021). Synthesis, characterization and computational study on potential inhibitory action of novel azo imidazole derivatives against COVID-19 main protease (Mpro: 6LU7). Journal of molecular structure1225, 129230.
[15] Ghasemi, L., Esfahani, M. H., Abbasi, A., & Behzad, M. (2022). Synthesis and crystal structures of new mixed-ligand schiff base complexes containing N-donor heterocyclic co-ligands: Molecular docking and pharmacophore modeling studies on the main proteases of SARS-CoV-2 virus (COVID-19 disease). Polyhedron220, 115825.
[16] Qiao, Z., Wei, N., Jin, L., Zhang, H., Luo, J., Zhang, Y., & Wang, K. (2021). The Mpro structure-based modifications of ebselen derivatives for improved antiviral activity against SARS-CoV-2 virus. Bioorganic Chemistry117, 105455.
[17] Sahoo, R. N., Pattanaik, S., Pattnaik, G., Mallick, S., & Mohapatra, R. (2022). Review on the use of Molecular Docking as the First Line Tool in Drug Discovery and Development. Indian Journal of Pharmaceutical Sciences84(5).
[18] Potluri, H., Prasanth, D. S., & Atmakuri, L. R. (2021). In vivo antinociceptive effect of methanolic extract of Ipomoea marginata Desr. in rodents as well as in silico molecular docking of some phytoconstituents from the plant. Indian J. Pharm. Sci83(4), 732-741.
[19] Parvarinezhad, S., & Salehi, M. (2024). New Metal Complexes Incorporating Schiff Base Ligand Based on Hydrazide Moiety: Synthesis, Spectral Characterization, Electrochemical behavior, and Molecular Docking. Applied Chemistry Today19(73), 253-268.
[20] Parvarinezhad, S., Salehi, M., & Kubicki, M. (2025). New dinuclear Schiff base nickel complex: Investigation of intermolecular interactions via theoretical calculations, molecular docking studies and ADMET profiling approaches survey. Journal of Molecular Structure1326, 141016.
[21] Parvarinezhad, S., Salehi, M., & Kubicki, M. (2022). Synthesis, characterization, spectral studies and evaluation of noncovalent interactions in co-crystal of μ-oxobridged polymeric copper (II) complex derived from pyrazolone by theoretical studies. Journal of Molecular Structure1260, 132780.
[22] Parvarinezhad, S., Salehi, M., Eshaghi Malekshah, R., Kubicki, M., & Khaleghian, A. (2022). Synthesis, characterization, spectral studies two new transition metal complexes derived from pyrazolone by theoretical studies, and investigate anti‐proliferative activity. Applied Organometallic Chemistry36(3), e6563.
[23] Parvarinezhad, S., & Salehi, M. (2023). New pyrazolone-based Schiff base Cu (II) complexes: Synthesis, spectra, theoretical calculation and protein binding. Applied Chemistry Today69(18), 113-136.
[24] Deshpande, R. R., Tiwari, A. P., Nyayanit, N., and Modak, M. (2020) In silico molecular docking analysis for repurposing therapeutics against multiple proteins from SARS-CoV-2. Eur. J. Pharmacol. 886, 173430.