Oral anticancer prediction of hexadecenoic acid on p50 target receptor by molecular docking
Keywords:
drug development, hexadecenoic acid, molecular docking, oral anticancer, human well-beingAbstract
Ambonese banana stem extract (Musa paradisiaca var. sapientum) has been proven to contain the active compound hexadecenoic acid (Hexa) which can suppress the growth of cancer cells through the apoptosis process. The aims to determine HA interaction to nuclear factor-kappa-B p50/ReLA for the development of oral anticancer drugs through molecular docking. In silico study carried out include prediction of activity spectra of substances (PASS), drug-likeness analysis based on the lipinski rule of five principles, absorption, distribution, metabolism, excretion, and toxicity (ADMET) study, molecular docking and HA bond visualization (CID: 985), along with the positive control comparison compound 5-fluorouracil (Fluo) (CID: 3385) and the derivative compound 9-octadecenoic acid (Octa) (CID: 445639) which bind to the proteins target RelA (PDB ID: 6NV2). Results data shows HA compounds have potential as anticancer therapy because of their distribution throughout the body and their activity against cancer. Molecular docking shows that HA is predicted to bind more effectively to the binding pocket of both RelA, while 9-octadecenoic acid has a fairly good interaction with RelA when compared to 5-Fluorouracil. From this study, we can conclude that Hexadecenoic acid compound found in Musa paradisiaca var. sapientum (L.) Kuntze represents a breakthrough in developing new drugs with potential and effectiveness against RelA/p50.
References
Dohude GA, Ramaliah R. Tingkat pengetahuan dokter gigi mengenai deteksi dini karsinoma sel skuamosa rongga mulut. Knowledge level of dentists about early detection and diagnosis of oral squamous cell carcinoma. Padjadjaran Journal of Dental Researchers and Students. 2022;6(2):137. https://doi.org/10.24198/pjdrs.v6i2.39540.
NCI (National Cancer Institute). Oral Squamous Cell Carcinoma Mutational Profile in Taiwanese Population. Diakses, 2023 September. https://proteomics.cancer.gov/news_and_announcements/oral-squamous-cell-carcinoma-mutational-profile-taiwanese-population.
Permata Sari R. Nindia Carabelly dan Maharani Laillyza Apriasari Program Studi Kedokteran Gigi, A., & Studi Kedokteran Gigi, P. 2012. 30 Aviandani dkk : Perbedaan kebocoran tepi tumpatan semen ionomer kaca Prevalensi lesi praganas pada mukosa mulut wanita lanjut usia dengan menginang di kecamatan Lokpaikat kabupaten Tapin periode Mei-Oktober 2013 (Premalignant lesion prevalence in oral mucosa of elderly women with betel quid chewing habit in sub Lopikat, Tapin district the period May to October 2013). https://123dok.com/document/qok48vmy-rima-permata-sari-nindia-carabelly-maharani-laillyza-apriasari.html
Yardimci G. Precancerous lesions of oral mucosa. World Journal of Clinical Cases. 2014;2(12):866. https://doi.org/10.12998/wjcc.v2.i12.866.
Rusanen P, Marttila E, Uittamo J, Hagström J, Salo T, Rautemaa-Richardson R. TLR1-10, NF-κB and p53 expression is increased in oral lichenoid disease. 2017;12(7):e0181361. https://doi.org/10.1371/journal.pone.0181361.
Pisani LP, Estadella D, Ribeiro DA. The role of toll like receptors (TLRs) in oral carcinogenesis. In Anticancer Research. 2017;37(10):5389-5394. https://doi.org/10.21873/anticanres.11965.
Palani CD, Ramanathapuram L, Lam-Ubol A, Kurago ZB. Toll-like receptor 2 induces adenosine receptor A2a and promotes human squamous carcinoma cell growth via extracellular signal regulated kinases ½. Oncotarget. 2017;9(6):6814-6829. https://doi.org/10.18632/oncotarget.23784.
Idrish M, Khan R. NF-kB (Nuclear Factor Kappa Beta)-A Cell Signalling Pathway, 2018. https://www.researchgate.net/publication/325803313.
Bu Y, Li X, He Y, Huang C, Shen Y, Cao Y, et al. A phosphomimetic mutant of RELA/p50 at S er536 induces apoptosis and senescence: An implication for tumor‐suppressive role of S er536 phosphorylation. International Journal of Cancer. 2016;138(5):1186-1198. 10.18632/oncotarget.17641.
Budi HS, Anitasari S, Ulfa NM, Juliastuti WS, Aljunaid M, Ramadan DE, et al. Topical Medicine Potency of Musa paradisiaca var sapientum (L.) kuntze as Oral Gel for Wound Healing: An in Vitro, in Vivo Study. European Journal of Dentistry. 2022;16(4):848-855. https://doi.org/10.1055/s-0041-1740226.
Adhayanti I, Abdullah T, Romantika R, Farmasi Poltekkes Kemenkes Makassar J. Uji Kandungan Total Polifenol Dan Flavonoid Ekstrak Etil Asetat Kulit Pisang Raja (Musa paradisiaca var. sapientum), 2018, 1. https://doi.org/10.32382/mf.v14i1.84.
Parrales A, Iwakuma T. p53 as a regulator of lipid metabolism in cancer. International Journal of Molecular Sciences. 2016;17(12):2074. 10.3390/ijms17122074.
Madden JC, Enoch SJ, Paini A, Cronin MTD. ‘A review of in silico tools as alternatives to Animal Testing: Principles, resources and applications’, Alternatives to Laboratory Animals. 2020;48(4):146-172. DOI: 10.1177/0261192920965977
Meng Q, Gao Q, Mehrazarin S, Tangwanichgapong K, Wang Y, Huang Y, et al. Fusobacterium Nucleatum Secretes Amyloid-Like FadA to Enhance Pathogenicity. 2021;22(7):e52891. 10.15252/embr.202152891.
Yasmin R, Mafiroh WU, Kinasih A, Ramadhani AN, Putri R, Semiarti E. Potential of Orchids Secondary Metabolites as Anti-Cancer and Antimicrobial Based on Prediction of Phytochemical Activity with Online PASS-Software. Journal of Agromedicine and Medical Sciences. 2022;8(1):25-33. 10.3389/fcimb.2022.815318.
Abdjan MI, Aminah NS, Siswanto I, Thant TM, Kristanti AN, Takaya Y. In silico approach: biological prediction of nordentatin derivatives as anticancer agent inhibitors in the cAMP pathway. RSC advances. 2020;10(70):42733-42743. 10.1039/d0ra07838g.
Nugraha AP, Sibero MT, Nugraha AP, Puspitaningrum MS, Rizqianti Y, Rahmadhani D, et al. Anti-Periodontopathogenic Ability of Mangrove Leaves (Aegiceras corniculatum) Ethanol Extract: In silico and in vitro study. European Journal of Dentistry. 2022;17(01):046-056. 10.1055/s-0041-1741374.
Chen Y, Huang Z, Tang Z, Huang Y, Huang M, Liu H, et al. More than just a periodontal pathogen–the research progress on Fusobacterium nucleatum. Frontiers in Cellular and Infection Microbiology. 2022;12:64. 10.3389/fcimb.2022.815318.
Karami TK, Hailu S, Feng S, Graham R, Gukasyan HJ. “Eyes on Lipinski’s Rule of Five: A New ‘Rule of Thumb’ for Physicochemical Design Space of Ophthalmic Drugs”, Journal of Ocular Pharmacology and Therapeutics: The Official Journal of the Association for Ocular Pharmacology and Therapeutics, J Ocul Pharmacol Ther. 2022;38(1):43-55. 10.1089/jop.2021.0069.
Trott O, Olson AJ. Autodock Vina: Improving the speed and accuracy of docking with a new scoring function, Efficient Optimization, and Multithreading. J Comput Chem. 2010;31:455-461. 10.1002/jcc.21334.
Dar AM, Mir S. Molecular Docking: Approaches, Types, Applications and Basic Challenges. Journal of Analytical & Bioanalytical Techniques. 2017;8(2):1-3. https://doi.org/10.4172/2155-9872.1000356.
Pinzi L, Rastelli G. “Molecular docking: shifting paradigms in drug discovery”, International Journal of Molecular Sciences, MDPI. 2019;20(18):4331. https://doi.org/10.3390/ijms20184331.
Izzaturrahmi AS. Studi In-Silico Tanaman Akar Manis (Glycyrrhiza glabra L.) terhadap Reseptor VEGFR-2 pada Kanker Payudara. Indonesian Journal of Biological Pharmacy, 2023, 3(3). https://doi.org/10.24198/ijbp.v3i3.45597.
Khaled DM, Elshakre ME, Noamaan MA, Butt H, Abdel Fattah MM, Gaber DA. A computational QSAR, molecular docking and in vitro cytotoxicity study of novel thiouracil-based drugs with anticancer activity against human-DNA topoisomerase II. International Journal of Molecular Sciences. 2023;23(19):11799. 10.3390/ijms231911799.
Coimbra JTS, Feghali R, Ribeiro RP, Ramos MJ, Fernandes PA. The importance of intramolecular hydrogen bonds on the translocation of the small drug piracetam through a lipid bilayer. RSC advances. 2021;11(2):899-908. https://doi.org/10.1039/d0ra09995c
Pitaloka AD, Nurhijriah CY, Kalina K, Musyaffa HA, Azzahra AM. Penambatan Molekuler Konstituen Kimia Tumbuhan Bawang Dayak (Eleutherine palmifolia (L.) Merr) terhadap Reseptor VHR sebagai Kandidat Obat Antikanker Serviks. Indonesian Journal of Biological Pharmacy. 2023;3(2):83-95. https://doi.org/10.24198/ijbp.v3i2.45221.
Ibrahim ZYU, Uzairu A, Shallangwa GA, Abechi SE. Pharmacokinetic predictions and docking studies of substituted aryl amine-based triazolopyrimidine designed inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH). Future Journal of Pharmaceutical Sciences. 2021;7:1-10. https://doi.org/10.1186/s43094-021-00288-2.
Egan PF, Stone JA, Scherschligt JK, Harvey AH. Measured relationship between thermodynamic pressure and refractivity for six candidate gases in laser barometry. Journal of Vacuum Science & Technology A, 2019, 37(3). https://doi.org/10.1116/1.5092185.
Lipinski CA. Lead-and drug-like compounds: the rule-of-five revolution. Drug discovery today: Technologies. 2004;1(4):337-341. 0.1016/j.ddtec.2004.11.007.
Ferreira LLG, Andricopulo AD. “ADMET modeling approaches in drug discovery”, Drug Discovery Today, Elsevier. 2019;24(5):1157-1165. 10.3389/fchem.2020.00726.
Kumar V, Kumar R, Parate S, Yoon S, Lee G, Kim D, et al. Identification of ACK1 inhibitors as anticancer agents by using computer-aided drug designing. Journal of Molecular Structure. 2021;1235:130200. 10.3390/biom13020217.
Lohohola PO, Mbala BM, Bambi SMN, Mawete DT, Matondo A, Mvondo JGM. In silico ADME/T properties of quinine derivatives using SwissADME and pkCSM webservers. International Journal of TROPICAL DISEASE & Health. 2021;42(11):1-12. 10.9734/ijtdh/2021/v42i1130492.
Firdausy AF, Mutiah R, Rahmawati EK. Predicting pharmacokinetic profiles of sunflower’s (Helianthus annuus L.) active compounds using in silico approach. Journal of Islamic Medicine. 2020;4(1):1-7. https://doi.org/10.18860/jim.v4i1.8840.
Shehzadi N, Hussain K, Islam M, Bukhari NI, Khan MT, Salman M, et al. In silico drug-qualifying parameters of 5-[(4-chlorophenoxy) methyl]-1, 3, 4-oxadiazole-2-thiol. Lat Am J Pharm. 2016;35:1991-97. 10.3329/bjp.v13i2.35514.
Rasyid H, Mardiyanti R, Arief I, Saputri WD. An Insight of Cryptocarya Secondary Metabolites as Anticancer P388: Study of Molecular Docking, ADMET Properties, and Molecular Dynamic Simulation, 2023. https://doi.org/10.20884/1.jm.2023.18.1.6364.
Savitri AD, Hidayati HB, Veterini L, Widyaswari MS, Muhammad AR, Fairus A, et al. An In-Silico Study on Allicin Compound in Garlic (Allium Sativum) as A Potential Inhibitor of Human Epidermal Growth Factor Receptor (Her)-2 Positive Breast Cancer. JJBS: Jordan Journal of Biological Sciences. 2023;16(1):7-12. http://repository.unusa.ac.id/id/eprint/8599.
Ugbe FA, Shallangwa GA, Uzairu A, Abdulkadir I. Theoretical activity prediction, structure-based design, molecular docking and pharmacokinetic studies of some maleimides against Leishmania donovani for the treatment of leishmaniasis. Bulletin of the National Research Centre. 2022;46(1):92. https://doi.org/10.1186/s42269-022-00779-z.
Benouchenne D, Bellil I, Tachour SH, Akkal S, Djeghim H, Kebaili FF, et al. Tyrosinase Inhibitory Ability and In Vitro, In Vivo Acute Oral and In Silico Toxicity Evaluation of Extracts Obtained from Algerian Fir (Abiesnumidica de Lannoy ex CARRIERE) Needles. Plants. 2022;11(18):2389. 10.3390/plants11182389.
Ferrari IV. Assessing Antibiotic Safety: A Comparative Study of Four Promising Candidates Using pKCSM Database, 2023. 10.20944/preprints202312.0894.v1.
Ma'arif B, Aminullah M, Saidah NL, Muslikh FA, Rahmawati A, Indrawijaya YYA, et al. Prediction of antiosteoporosis activity of thirty-nine phytoestrogen compounds in estrogen receptor-dependent manner through in silico approach. Tropical Journal of Natural Product Research. 2021;5(10):1727-1734. http://www.tjnpr.org/viewarticle.aspx?articleid=19
Perumalsamy H, Sankarapandian K, Veerappan K, Natarajan S, Kandaswamy N, Thangavelu L, et al. In silico and in vitro analysis of coumarin derivative induced anticancer effects by undergoing intrinsic pathway mediated apoptosis in human stomach cancer. Phytomedicine. 2018;46:119-130. 10.1016/j.phymed.2018.04.021.
Chy MNU, Chakrabarty N, Roy A, Paul A, Emu KA, Dutta T, et al. Antibacterial, anthelmintic, and analgesic activities of Piper sylvaticum (Roxb.) leaves and in silico molecular docking and PASS prediction studies of its isolated compounds. Journal of Complementary & Integrative Medicine, 2019, 16(4). https://doi.org/10.1515/JCIM-2018-0176.
Saharani SM, Yuniastuti A, Susanti R. Identifikasi Senyawa Bioaktif Tanaman Syzygium aromaticum Sebagai Imunostimulan Melalui Toll-Like Receptor Signaling Pathway Berdasarkan Interaksi Senyawa-Protein Secara In Silico. In Seminar Nasional Biologi. 2021;9:310-316.
Chen D, Oezguen N, Urvil P, Ferguson C, Dann SM, Savidge TC. Regulation of protein-ligand binding affinity by hydrogen bond pairing. Science advances. 2016;2(3):e1501240. https://doi.org/10.1126/sciadv.1501240.
Jayaraman L, Shivaji S, Anandakumar S. Phytochemical screening, cytotoxic activity and molecular docking studies of Eclipta alba leaves extract against oral cancer. Rasayan J. Chem. 2022;15:676-685. https://proceeding.unnes.ac.id/semnasbiologi/article/view/801/709
Aruleba RT, Adekiya TA, Oyinloye BE, Kappo AP. Structural studies of predicted ligand binding sites and molecular docking analysis of Slc2a4 as a therapeutic target for the treatment of cancer. International Journal of Molecular Sciences. 2018;19(2):386. 10.3390/ijms19020386.
Shah HD, Saranath D, Murthy V. A molecular dynamics and docking study to screen anti-cancer compounds targeting mutated p53. Journal of Biomolecular Structure and Dynamics, 2022, 40(6). 10.1080/07391102.2020.1839559.
