ADME-Tox profile of Cuminaldehyde (4-Isopropylbenzaldehyde) from Cuminum cyminum seeds for potential biomedical applications
Abstract
Cuminum cyminum L (Family: Apiaceae) is a small multipurpose herb. Seeds of cumin are widely used as a spice for its distinctive aroma, and more commonly in various indigenous traditional systems of medicine. Access through web literature provides ample evidence for biomedical activities of Cuminum cyminum seeds (CCS). CCS has been used in traditional medicine to treat variety of diseases, including hypolipidemia, cancer, and diabetes. Biomedical properties of CCS is attributed to its phytochemical class of compounds viz., terpenes, phenols and flavonoids. Health effects of CCS have been experimentally validated through phytochemical screening deciphering the fact that it contains a large number of bioactive secondary metabolites (BASMs) viz., alkaloid, coumarin, anthraquinones, flavonoid, glycoside, protein, resin, saponin, tannin and steroid. Furthermore, pharmacological studies indicate that BASMs in CCS exert antimicrobial, insecticidal, anti-inflammatory, analgesic, antioxidant, anticancer, antidiabetic, anti-platelet-aggregation, hypotensive, bronchodilatory, immunological, contraceptive, anti-amyloidogenic, anti-osteoporotic, aldose reductase, α-glucosidase and tyrosinase inhibitory effects. Cuminaldehyde is one of the major bioactive compounds in CCS that holds significant pharmacological prominence. However, in-depth studies are lacking henceforth warranted to elucidate and fill the gaps, particularly on phytocompound isolation, pre-clinical, clinical characterization, and evaluation of structure–activity relationship. The present study prospects ADMETox perspectives of cuminaldehyde (4-Isopropylbenzaldehyde).
Keywords: Cuminaldehyde; Isopropylbenzaldehyde; Cuminum cyminum; ADMETox; Natural Product (NP)
Keywords:
Cuminaldehyde, Isopropylbenzaldehyde, Cuminum cyminum, ADMETox, Natural Product (NP)DOI
https://doi.org/10.22270/jddt.v12i2-S.5286References
Attene-Ramos, M., R. Huang, S. Michael, K. Witt, A. Richard, R. Tice, A. Simeonov, C. Austin, M. Xia. Profiling of the Tox21 chemical collection for mitochondrial function to identify compounds that acutely decrease mitochondrial membrane potential. 2015; 123(1):49. https://doi.org/10.1289/ehp.1408642
Broccatelli, F., E. Carosati, A. Neri, M. Frosini, L. Goracci, T. Oprea, and G. Cruciani. A novel approach for predicting P-Glycoprotein (ABCB1) inhibition using molecular interaction fields. 2011; 54(6):1740-1751. https://doi.org/10.1021/jm101421d
Caldwell GW, Yan Z, Tang W, Dasgupta M, Hasting B. ADME optimization and toxicity assessment in early-and late-phase drug discovery. Current topics in medicinal chemistry. 2009; 9(11):965-80. https://doi.org/10.2174/156802609789630929
Chen, L., Y. Li, Q. Zhao, H. Peng, and T. Hou. ADME evaluation in drug discovery. 10. Predictions of P-Glycoprotein inhibitors using recursive partitioning and naive bayesian classification techniques. 2011; 8(3):889-900. https://doi.org/10.1021/mp100465q
Cheng F, Li W, Liu G, Tang Y. In silico ADMET prediction: recent advances, current challenges and future trends. Current topics in medicinal chemistry. 2013; 13(11):1273-89. https://doi.org/10.2174/15680266113139990033
Ferreira LL, Andricopulo AD. ADMET modelling approaches in drug discovery. Drug discovery today. 2019; 24(5):1157-1165. https://doi.org/10.1016/j.drudis.2019.03.015
Cook D, Brown D, Alexander R, March R, Morgan P, Satterthwaite G, Pangalos MN. Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework. Nature reviews Drug discovery. 2014; 13(6):419-431. https://doi.org/10.1038/nrd4309
Yu H, Adedoyin A. ADME-Tox in drug discovery: integration of experimental and computational technologies. Drug discovery today. 2003; 8(18):852-61. https://doi.org/10.1016/S1359-6446(03)02828-9
Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates?. Nature reviews Drug discovery. 2004; 3(8):711-6. https://doi.org/10.1038/nrd1470
Yang H, Sun L, Li W, Liu G, Tang Y. In silico prediction of chemical toxicity for drug design using machine learning methods and structural alerts. Frontiers in chemistry. 2018; 6:30. https://doi.org/10.3389/fchem.2018.00030
Kandeepan C, Kalaimathi RV, Jeevalatha A, Basha AN, Ramya S, Jayakumararaj R. In-silico ADMET Pharmacoinformatics of Geraniol (3,7-dimethylocta-trans-2,6-dien-1-ol)-acyclic monoterpene alcohol drug from Leaf Essential Oil of Cymbopogon martinii from Sirumalai Hills (Eastern Ghats), INDIA. Journal of Drug Delivery and Therapeutics. 2021; 11(4-S):109-18. https://doi.org/10.22270/jddt.v11i4-S.4965
Li, D., L. Chen, Y. Li, S. Tian, H. Sun, and T. Hou. ADMET evaluation in drug discovery. Development of in Silico prediction models for P-Glycoprotein substrates. 2014; 11(3):716-726. https://doi.org/10.1021/mp400450m
Loganathan T, Barathinivas A, Soorya C, Balamurugan S, Nagajothi TG, Ramya S, Jayakumararaj R. Physicochemical, Druggable, ADMET Pharmacoinformatics and Therapeutic Potentials of Azadirachtin-a Prenol Lipid (Triterpenoid) from Seed Oil Extracts of Azadirachta indica A. Juss. Journal of Drug Delivery and Therapeutics. 2021; 11(5):33-46. https://doi.org/10.22270/jddt.v11i5.4981
Schyman, P., R. Liu, V. Desai, and A. Wallqvist. vNN web server for ADMET predictions. Frontiers in Pharmacology. 2017; 8:889. https://doi.org/10.3389/fphar.2017.00889
Selick HE, Beresford AP, Tarbit MH. The emerging importance of predictive ADME simulation in drug discovery. Drug Discovery Today. 2002; 7(2):109-16. https://doi.org/10.1016/S1359-6446(01)02100-6
Sabitha M, Krishnaveni K, Murugan M, Basha AN, Pallan GA, Kandeepan C, Ramya S, Jayakumararaj R. In-silico ADMET predicated Pharmacoinformatics of Quercetin-3-Galactoside, polyphenolic compound from Azadirachta indica, a sacred tree from Hill Temple in Alagarkovil Reserve Forest, Eastern Ghats, INDIA. Journal of Drug Delivery and Therapeutics. 2021; 11(5-S):77-84. https://doi.org/10.22270/jddt.v11i5-S.5026
Soorya C, Balamurugan S, Ramya S, Neethirajan K, Kandeepan C, Jayakumararaj R. Physicochemical, ADMET and Druggable properties of Myricetin: A Key Flavonoid in Syzygium cumini that regulates metabolic inflammations. Journal of Drug Delivery and Therapeutics. 2021; 11(4):66-73. https://doi.org/10.22270/jddt.v11i4.4890
Ramya S, Soorya C, Sundari A, Grace Lydial Pushpalatha G, Aruna D, Loganathan T, Balamurugan S, Abraham GC, Ponrathy T, Kandeepan C, Jayakumararaj R, Artificial Intelligence and Machine Learning approach based in-silico ADME-Tox and Pharmacokinetic Profile of α-Linolenic acid from Catharanthus roseus (L.) G. Don., Journal of Drug Delivery and Therapeutics. 2022; 12(2-s):96-109. https://doi.org/10.22270/jddt.v12i2-S.5274
Cragg GM, Newman DJ. Natural products: a continuing source of novel drug leads. Biochimica et Biophysica Acta (BBA)-General Subjects. 2013 Jun 1; 1830(6):3670-95. https://doi.org/10.1016/j.bbagen.2013.02.008
Thomford NE, Senthebane DA, Rowe A, Munro D, Seele P, Maroyi A, Dzobo K. Natural products for drug discovery in the 21st century: innovations for novel drug discovery. International journal of molecular sciences 2018; 19(6):1578. https://doi.org/10.3390/ijms19061578
Newman DJ, Cragg GM. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. Journal of Natural Products. 2020; 83(3):770-803. https://doi.org/10.1021/acs.jnatprod.9b01285
Atanasov AG, Zotchev SB, Dirsch VM, Supuran CT. Natural products in drug discovery: advances and opportunities. Nature Reviews Drug Discovery 2021; 20(3):200-16. https://doi.org/10.1038/s41573-020-00114-z
Shanmugam S, Sundari A, Muneeswaran S, Vasanth C, Jayakumararaj R, Rajendran K. Ethnobotanical indices on medicinal plants used to treat poisonous bites in Thiruppuvanam region of Sivagangai district in Tamil Nadu, India. Journal of Drug Delivery and Therapeutics. 2020; 10(6-s):31-36. https://doi.org/10.22270/jddt.v10i6-s.4432
Kadhirvel K, Ramya S, Sudha TS, Ravi AV, Rajasekaran C, Selvi RV, Jayakumararaj R. Ethnomedicinal survey on plants used by tribals in Chitteri Hills. Environ We Int J Sci Tech. 2010; 5:35-46.
Kalaivani T, Premkumar N, Ramya S, Siva R, Vijayakumar V, Meignanam E, Rajasekaran C, Jayakumararaj R. Investigations on hepatoprotective activity of leaf extracts of Aegle marmelos (L.) Corr. (Rutaceae). Ethnobotanical leaflets. 2009; 2009(1):4.
Ramya S, Alaguchamy N, Maruthappan VM, Sivaperumal R, Sivalingam M, Krishnan A, Govindaraji V, Kannan K, Jayakumararaj R. Wound healing ethnomedicinal plants popular among the Malayali tribes in Vattal Hills, Dharmapuri, TN, India. Ethnobotanical Leaflets. 2009; 2009(10):6.
Ramya S, Jayakumararaj R. Antifeedant activity of selected ethno-botanicals used by tribals of Vattal Hills on Helicoverpa armigera (Hübner). Journal of Pharmacy Research. 2009; 2(8):1414-8.
Ramya S, Jepachanderamohan PJ, Kalayanasundaram M, Jayakumararaj R. In vitro antibacterial prospective of crude leaf extracts of Melia azedarach Linn. against selected bacterial strains. Ethnobotanical Leaflets. 2009; 2009(1):32.
Ramya S, Krishnasamy G, Jayakumararaj R, Periathambi N, Devaraj A. Bioprospecting Solanum nigrum Linn.(Solanaceae) as a potential source of Anti-Microbial agents against selected Bacterial strains. Asian Journal of Biomedical and Pharmaceutical Sciences. 2012; 2(12):65.
Ramya S, Neethirajan K, Jayakumararaj R. Profile of bioactive compounds in Syzygium cumini-a review. Journal of Pharmacy research. 2012; 5(8):4548-53.
Sivaperumal R, Ramya S, Ravi AV, Rajasekaran C, Jayakumararaj R. Herbal remedies practiced by Malayali's to treat skin diseases. Environ We Int J Sci Tech. 2009; 4(1):35-44.
Sivaperumal R, Ramya S, Ravi AV, Rajasekaran C, Jayakumararaj R. Ethnopharmacological studies on the medicinal plants used by tribal inhabitants of Kottur Hills, Dharmapuri, Tamilnadu, India. Environ We Int J Sci Technol. 2010; 5:57-64.
Soorya C, Balamurugan S, Basha AN, Kandeepan C, Ramya S, Jayakumararaj R. Profile of Bioactive Phyto-compounds in Essential Oil of Cymbopogon martinii from Palani Hills, Western Ghats, INDIA. Journal of Drug Delivery and Therapeutics. 2021; 11(4):60-5. https://doi.org/10.22270/jddt.v11i4.4887
Sundari A, Jayakumararaj R. Herbal remedies used to treat skin disorders in Arasankulam region of Thoothukudi District in Tamil Nadu, India. Journal of Drug Delivery and Therapeutics. 2020; 10(5):33-38. https://doi.org/10.22270/jddt.v10i5.4277
Sundari A, Jayakumarbaraj R. Medicinal plants used to cure cuts and wounds in Athur region of Thoothukudi district in Tamil Nadu, India. Journal of Drug Delivery and Therapeutics. 2020; 10(6-s):26-30. https://doi.org/10.22270/jddt.v10i6-s.4429
Yuan H, Ma Q, Ye L, Piao G. The traditional medicine and modern medicine from natural products. Molecules. 2016; 21(5):559. https://doi.org/10.3390/molecules21050559
Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, Linder T, Wawrosch C, Uhrin P, Temml V, Wang L, Schwaiger S, Heiss EH, Rollinger JM. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnology advances 2015; 33(8):1582-614. https://doi.org/10.1016/j.biotechadv.2015.08.001
Omari Z, Kazunori S, Sabti M, Bejaoui M, Hafidi A, Gadhi C, Isoda H. Dietary administration of cumin-derived cuminaldehyde induce neuroprotective and learning and memory enhancement effects to aging mice. Aging (Albany NY). 2021; 13(2):1671. https://doi.org/10.18632/aging.202516
Al-Snafi AE. The pharmacological activities of Cuminum cyminum A review. IOSR Journal of Pharmacy. 2016; 6(6):46-65.
Mnif S, Aifa S. Cumin (Cuminum cyminum L.) from traditional uses to potential biomedical applications. Chemistry & biodiversity. 2015 May; 12(5):733-42. https://doi.org/10.1002/cbdv.201400305
Patel CN, Kumar SP, Rawal RM, Patel DP, Gonzalez FJ, Pandya HA. A multi-parametric organ toxicity predictor for drug discovery. Toxicology mechanisms and methods. 2020; 30(3):159-66. https://doi.org/10.1080/15376516.2019.1681044
Ramya S, Loganathan T, Chandran M, Priyanka R, Kavipriya D, Grace Lydial Pushpalatha G, Aruna D, Ramanathan L, Jayakumararaj R, Phytochemical Screening, GCMS, FTIR profile of Bioactive Natural Products in the methanolic extracts of Cuminum cyminum seeds and oil, Journal of Drug Delivery and Therapeutics. 2022; 12(2-s):110-118. https://doi.org/10.22270/jddt.v12i2-S.5280
Nyberg L, Backman L. Cognitive ageing: a view from brain imaging. In: Dixon R, Backman L, Nilsson L, Eds. New frontiers in cognitive ageing. Oxford University Press, 2004; 135-60. https://doi.org/10.1093/acprof:oso/9780198525691.003.0007
Ebada ME. Cuminaldehyde: A potential drug candidate. J Pharmacol Clin Res. 2017; 2(2):1-4. https://doi.org/10.19080/JPCR.2017.02.555585
Jabeen NS, Jagapriya L, Senthilkumar B, Devi K. Challenging Compounds of Some Medicinal Plants against Cancer. Drug Development for Cancer and Diabetes: A Path to 2030. 2020 Aug 30:95. https://doi.org/10.1201/9780429330490-8
Tomy MJ, Dileep KV, Prasanth S, Preethidan DS, Sabu A, Sadasivan C, Haridas M. Cuminaldehyde as a lipoxygenase inhibitor: in vitro and in silico validation. Applied biochemistry and biotechnology. 2014 Sep; 174(1):388-97. https://doi.org/10.1007/s12010-014-1066-0
Monteiro-Neto V, de Souza CD, Gonzaga LF, da Silveira BC, Sousa NC, Pontes JP, Santos DM, Martins WC, Pessoa JF, Carvalho Junior AR, Almeida VS. Cuminaldehyde potentiates the antimicrobial actions of ciprofloxacin against Staphylococcus aureus and Escherichia coli. PLoS One. 2020 May 14; 15(5):e0232987. https://doi.org/10.1371/journal.pone.0232987
Hassan HA, Genaidy MM, Kamel MS, Abdelwahab SF. Synergistic antifungal activity of mixtures of clove, cumin and caraway essential oils and their major active components. Journal of Herbal Medicine. 2020 Dec 1; 24:100399. https://doi.org/10.1016/j.hermed.2020.100399
Morshedi D, Aliakbari F, Tayaranian‐Marvian A, Fassihi A, Pan‐Montojo F, Pérez‐Sánchez H. Cuminaldehyde as the major component of Cuminum cyminum, a natural aldehyde with inhibitory effect on alpha‐synuclein fibrillation and cytotoxicity. Journal of food science. 2015; 80(10):H2336-45. https://doi.org/10.1111/1750-3841.13016
Xu, Y., Z. Dai, F. Chen, S. Gao, J. Pei, and L. Lai. Deep learning for drug-induced liver injury. 2015; 55 (10):2085-2093 https://doi.org/10.1021/acs.jcim.5b00238
Liu, R., and A. Wallqvist. Merging applicability domains for in silico assessment of chemical mutagenicity. Journal of Chemical Information and Modelling. 2014; 54(3):793-800. https://doi.org/10.1021/ci500016v
Liu, R., P. Schyman, and A. Wallqvist. Critically assessing the predictive power of QSAR models for human liver microsomal stability. Journal of Chemical Information and Modelling. 2015; 55(8):1566-1575. https://doi.org/10.1021/acs.jcim.5b00255
Loganathan T, Barathinivas A, Soorya C, Balamurugan S, Nagajothi TG, Jayakumararaj R. GCMS Profile of Bioactive Secondary Metabolites with Therapeutic Potential in the Ethanolic Leaf Extracts of Azadirachta indica: A Sacred Traditional Medicinal Plant of INDIA. Journal of Drug Delivery and Therapeutics. 2021; 11(4-S):119-26. https://doi.org/10.22270/jddt.v11i4-S.4967
Muehlbacher, M., G. Spitzer, K. Liedl, J. Kornhuber. Qualitative prediction of blood-brain barrier permeability on a large and refined dataset. Journal of Computer-Aided Molecular Design. 2011; 25:1095. https://doi.org/10.1007/s10822-011-9478-1
Naef R. A generally applicable computer algorithm based on the group additively method for the calculation of seven molecular descriptors: Heat of combustion, LogPO/W, LogS, refractivity, polarizability, toxicity and LogBB of organic compounds; scope and limits of applicability. Molecules. 2015; 20(10):18279-351. https://doi.org/10.3390/molecules201018279
Schyman, P., R. Liu, and A. Wallqvist. Using the variable-nearest neighbour method to identify P-glycoprotein substrates and inhibitors. ACS Omega. 2016; 1(5):923-929. https://doi.org/10.1021/acsomega.6b00247
Schyman, P., R. Liu, and A. Wallqvist. General purpose 2D and 3D similarity approach to identify hERG blockers. Journal of Chemical Information and Modelling. 2016; 56(1):213-222. https://doi.org/10.1021/acs.jcim.5b00616
Liu, R., G. Tawa, and A. Wallqvist. Locally weighted learning methods for predicting dose-dependent toxicity with application to the human maximum recommended daily dose. Chemical Research in Toxicology. 2012; 25(10):2216-2226
Published



How to Cite
Issue
Section
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).