تصميم وتصنيع وفحص النشاط البيولوجي لمشتقات مركب كونيفيريل ألدهيد كمركبات محتملة مضادة للسرطان والأكسدة
DOI:
https://doi.org/10.35516/jjps.v16i2.1463الكلمات المفتاحية:
كونيفيريل ألدهيد، مضاد للسرطان، مضاد للأكسدة، DPPHالملخص
من المعروف أن النواتج الطبيعية تملك أنشطة مضادة للميكروبات والسرطان والأكسدة. من بين هذه النواتج الطبيعية هي القرفة التي تحتوي على مركب سينامالديهيد. وجدت الدراسات أن مركب السينامالديهايد ومشتقاته لهم أنشطة مضادة للسرطان والأكسدة. كما أظهر مركب كونيفيريل ألدهيد، وهو مركب غير سام للخلايا ومشتق من مركب سينامالديهايد، أن له نشاطا مضادا للسرطان. في هذه الدراسة، تم تصنيع عدد من مشتقات مركب كونيفيريل ألدهيد وتقييم أنشطتها المضادة للسرطان والأكسدة. أظهرت المركبات 1 و2 و4 و8-11 نشاطا ساما للخلايا ضد خلايا H1299، وهي خلايا سرطان الرئة ذات الخلايا غير الصغيرة، وأظهر مركب 4 أعلى فعالية لقتل الخلايا حيث بلغت قيمة نصف التركيز المثبط الأقصى 6.7 ميكرومولار. كما أظهرت مركبات 1 و2 و4 نشاطا مضاد للأكسدة بالمقارنة مع فيتامين سي، حيث وصلت نسبة الكسح للمركبات نصف نسبة الكسح لفيتامين سي في جميع التركيزات التي تم اختبارها للمركبات، وذلك من خلال تجربة فحص مضادات الأكسدة باستخدام مركب DPPH. أظهر مركب كونيفيريل ألدهيد نفسه نشاطا مضادا للأكسدة يعتمد على الجرعة، حيث من المقترح أن ذلك تم عن طريق آلية تثبيت الشوارد الحرة في المركب. وهكذا، أظهرت دراستنا أن مشتقات مركب كونيفيريل ألدهيد تظهر أنشطة مضادة للسرطان والأكسدة، والتي قد تمثل مركبات علاجية محتملة.
المراجع
(1) Kim, C, Kim, B. Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review. Nutrients 2018, 10 (8).
(2) Xu, D. P, Li, Y, Meng, X. et al. Natural Antioxidants in Foods and Medicinal Plants: Extraction, Assessment and Resources. International Journal of molecular sciences 2017, 18 (1).
(3) Kokoska, L, Kloucek, P, Leuner, O. et al. Plant-Derived Products as Antibacterial and Antifungal Agents in Human Health Care. Current medicinal chemistry 2019, 26 (29), 5501-5541.
(4) Heard, S. C, Wu, G, Winter, J. M. Antifungal natural products. Current opinion in biotechnology 2021, 69, 232-241.
(5) Alsalman, A. H, Aboalhaija, N, Talib, W.et al. Evaluation of the Single and Combined Antibacterial Efficiency of the Leaf Essential Oils of Four Common Culinary herbs: Dill, Celery, Coriander and Fennel Grown in Jordan. Journal of Essential Oil Bearing Plants 2021, 24 (2), 317-328.
(6) Abaza, I, Aboalhaija, N, Alsalman, A. et al.Aroma Profile, Chemical Composition and Antiproliferative Activity of the Hydrodistilled Essential Oil of a Rare Salvia Species (Salvia greggii). Journal of Biologically Active Products from Nature 2021, 11 (2), 129-137.
(7) Farah, A. I, Ahmad, M. N, Al-Qirim, T. M. The Antioxidant and Pro-oxidant Impacts of Varying Levels of Alpha-Lipoic Acid on Biomarkers of Myoglobin Oxidation in Vitro. Jordan Journal of Agricultural Sciences 2020, 16 (4), 89-99.
(8) Al-Qirim, T. M, Zafir, A, Banu, N. Comparative anti-oxidant potential of Rauwolfia serpentina and Withania somnifera on cardiac tissues. The FASEB Journal 2007, 21 (5), A271-A271.
(9) Dilshad, R, Batool, R. Antibacterial and Antioxidant Potential of Ziziphus jujube, Fagonia Arabica, Mallotus phillipensis and Hemidesmus Indicus. Jordan j pharm. Sci. 2022, 15 (3), 413-427.
(10) Femi-Oyewo, M. N, Adeleye, O. A, Bakre, L. G. et al. Evaluation of the Antimicrobial Activity of Strombosia grandifolia Hook.f. ex Benth Extract Hand Sanitizer Formulation. Jordan j pharm. Sci. 2023, 16 (1), 61-71.
(11) Naskar, A, Dasgupta, A, Acharya, K. Antioxidant and Cytotoxic Activity of Lentinus fasciatus. Jordan j pharm. Sci. 2023, 16 (1), 72-81.
(12) Shreaz, S, Wani, W. A, Behbehani, J. M. et al. Cinnamaldehyde and its derivatives, a novel class of antifungal agents. Fitoterapia 2016, 112, 116-31.
(13) Vasconcelos, N. G, Croda, J, Simionatto, S. Antibacterial mechanisms of cinnamon and its constituents: A review. Microbial pathogenesis 2018, 120, 198-203.
(14) Hong, S. H, Ismail, I. A, Kang, S. M. et al. Cinnamaldehydes in Cancer Chemotherapy. Phytotherapy research : PTR 2016, 30 (5), 754-67.
(15) Gan, F. F, Chua, Y. S. Scarmagnani, S, et al. Structure-activity analysis of 2'-modified cinnamaldehyde analogues as potential anticancer agents. Biochemical and biophysical research communications 2009, 387 (4), 741-7.
(16) Kostrzewa, T, Przychodzen, P, Gorska-Ponikowska , M. et al.Curcumin and Cinnamaldehyde as PTP1B Inhibitors With Antidiabetic and Anticancer Potential. Anticancer research 2019, 39 (2), 745-749.
(17) Warsito, W, Murlistyarini, S, Suratmo, S.et al. Molecular Docking Compounds of Cinnamaldehyde Derivatives as Anticancer Agents. Asian Pacific Journal of cancer prevention: APJCP 2021, 22 (8), 2409-2419.
(18) Hariri, M, Ghiasvand, R. Cinnamon and Chronic Diseases. Advances in experimental medicine and biology 2016, 929, 1-24.
(19) Mrityunjaya, M, Pavithra, V, Neelam, R.et al. Immune-Boosting, Antioxidant and Anti-inflammatory Food Supplements Targeting Pathogenesis of COVID-19. Frontiers in immunology 2020, 11, 570122.
(20) Tanaka, Y, Uchi, H, Furue, M. Antioxidant cinnamaldehyde attenuates UVB-induced photoaging. Journal of dermatological science 2019, 96 (3), 151-158.
(21) Hashimoto-Hachiya, A, Tsuji, G, Furue, M. Antioxidants cinnamaldehyde and Galactomyces fermentation filtrate downregulate senescence marker CDKN2A/p16INK4A via NRF2 activation in keratinocytes. Journal of dermatological science 2019, 96 (1), 53-56.
(22) Zhang, J. H, Liu, L. Q, He, Y. L. et al.Cytotoxic effect of trans-cinnamaldehyde on human leukemia K562 cells. Acta pharmacologica Sinica 2010, 31 (7), 861-6.
(23) Najar, B, Shortrede, J. E, Pistelli, L. et al.Chemical Composition and in Vitro Cytotoxic Screening of Sixteen Commercial Essential Oils on Five Cancer Cell Lines. Chemistry & biodiversity 2020, 17 (1), e1900478.
(24) Yu, C, Liu, S.L, Qi, M.H. et al.Cinnamaldehyde/ chemotherapeutic agents interaction and drug-metabolizing genes in colorectal cancer. Molecular medicine reports 2014, 9 (2), 669-76.
(25) Park, J, Baek, S. H. Combination Therapy with Cinnamaldehyde and Hyperthermia Induces Apoptosis of A549 Non-Small Cell Lung Carcinoma Cells via Regulation of Reactive Oxygen Species and Mitogen-Activated Protein Kinase Family. International journal of molecular sciences 2020, 21 (17).
(26) Abbasi, A, Hajialyani, M, Hosseinzadeh, L. et al. Evaluation of the cytotoxic and apoptogenic effects of cinnamaldehyde on U87MG cells alone and in combination with doxorubicin. Research in pharmaceutical sciences 2020, 15 (1), 26-35.
(27) Zhu, R, Liu, H, Liu, C. et al. Cinnamaldehyde in diabetes: A review of pharmacology, pharmacokinetics and safety. Pharmacological research 2017, 122, 78-89.
(28) Xu, R, Xiao, X, Zhang, S. et al.The methyltransferase METTL3-mediated fatty acid metabolism revealed the mechanism of cinnamaldehyde on alleviating steatosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2022, 153, 113367.
(29) Doyle, A. A, Stephens, J. C. A review of cinnamaldehyde and its derivatives as antibacterial agents. Fitoterapia 2019, 139, 104405.
(30) Du, G. F, Yin, X. F, Yang, D. H. et al. Proteomic Investigation of the Antibacterial Mechanism of trans-Cinnamaldehyde against Escherichia coli. Journal of proteome research 2021, 20 (5), 2319-2328.
(31) Yin, L, Chen, J, Wang, K. et al.Study the antibacterial mechanism of cinnamaldehyde against drug-resistant Aeromonas hydrophila in vitro. Microbial pathogenesis 2020, 145, 104208.
(32) Taguchi, Y, Hasumi, Y, Abe, S. et al. The effect of cinnamaldehyde on the growth and morphology of Candida albicans. Medical molecular morphology 2013, 46 (1), 8-13.
(33) Manneck, D, Manz, G, Braun, H. S. et al. The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO(3)(-) by the Porcine Colon. International Journal of molecular sciences 2021, 22 (10).
(34) Załuski, D, Cieśla, Ł, Janeczko, Z. The structure–activity relationships of plant secondary metabolites with antimicrobial, free radical scavenging and inhibitory activity toward selected enzymes. Studies in Natural Products Chemistry 2015, 45, 217-249.
(35) Ibrahim, A. I. M, Ikhmais, B, Batlle, E. et al. Design, Synthesis, Biological Evaluation and In Silico Study of Benzyloxybenzaldehyde Derivatives as Selective ALDH1A3 Inhibitors. Molecules 2021, 26 (19), 5770.
(36) Sudanich, S, Tiyaworanant, S, Yenjai, C. Cytotoxicity of flavonoids and isoflavonoids from Crotalaria bracteata. Natural product research 2017, 31 (22), 2641-2646.
(37) Cabello, C. M, Bair, W. B., Lamore, S. D. et al.The cinnamon-derived Michael acceptor cinnamic aldehyde impairs melanoma cell proliferation, invasiveness, and tumor growth. Free radical biology & medicine 2009, 46 (2), 220-31.
(38) Nair, A. S, Singh, A. K, Kumar, A.et al. FDA-Approved Trifluoromethyl Group-Containing Drugs: A Review of 20 Years. Processes 2022, 10 (10), 2054.
(39) Alkadi, H. A Review on Free Radicals and Antioxidants. Infectious disorders drug targets 2020, 20 (1), 16-26.
(40) Brand-Williams, W, Cuvelier, M. E, Berset, C. Use of a free radical method to evaluate antioxidant activity. LWT - Food Science and Technology 1995, 28 (1), 25-30.
(41) Kedare, S. B, Singh, R. P. Genesis and development of DPPH method of antioxidant assay. Journal of food science and technology 2011, 48 (4), 412-22.
(42) Caritá, A. C, Fonseca-Santos, B, Shultz, J. D.et al. Vitamin C: One compound, several uses. Advances for delivery, efficiency and stability. Nanomedicine: nanotechnology, biology, and medicine 2020, 24, 102117.
(43) Williams, F. M. Clinical significance of esterases in man. Clinical pharmacokinetics 1985, 10 (5), 392-403.
(44) Azhari, S, Xu, Y. S, Jiang, Q. X.et al. Physicochemical properties and chemical composition of Seinat (Cucumis melo var. tibish) seed oil and its antioxidant activity. Grasas y Aceites 2014, 65 (1), e008.
