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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Karanjin, A Promising Bioactive Compound Possessing Anti-cancer Activity against Experimental Model of Non-small Cell Lung Cancer Cells

Author(s): Gourav Kumar*, Dev Mani Pandey, Manik Ghosh, Stefano Dall'Acqua, Rashmi Gupta, Nishi Prakash Tiwari, Usman Mohd Siddique, Leena Vishwakrama, Sunil Kant Guleri, Uma Ranjan Lal and Supriya Dubey

Volume 24, Issue 5, 2024

Published on: 06 November, 2023

Page: [317 - 333] Pages: 17

DOI: 10.2174/0118715206255557231024095245

Price: $65

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Abstract

Aims: The aim of this study is to isolate the Millettia pinnata (Karanj) leaf extract for pure compound with anticancer properties and to study the molecular target of the isolates in non-small cell lung cancer cell lines.

Background: In our earlier research Millettia pinnata leaf extract has demonstrated potential anticancer activities. Thus, in pursuit of the bioactive compounds, the most potential active extract from our previous study was purified. Furthermore, the anticancer properties of the isolated compound karanjin was studied and aimed for apoptosis and restraining growth.

Methods: A novel method was developed through column chromatography for isolation and purification of the compound karanjin from leaf chloroform extract. The purified component was then characterised using FTIR, mass spectrometry, and NMR. An MTT-based cytotoxicity assay was used to analyse cell cytotoxicity, whereas fluorescence staining was used for apoptosis and reactive oxygen species inhibition quantification. Furthermore, the real-time PCR assay was used to determine the molecular mechanism of action in cells causing cytotoxicity induced by karanjin dosing.

Results: The anticancer activity of karanjin in A549 cell line exhibited prominent activity revealing IC50 value of 4.85 μM. Conferring the predicted molecular pathway study, karanjin restrains the proliferation of cancer cells through apoptosis, which is controlled by extrinsic pathway proteins FAS/FADD/Caspases 8/3/9. Downregulation of KRAS and dependent gene expression also stopped cell proliferation.

Conclusion: Karanjin has been identified as a compound with potential effect in non-small cell lung cancer cells. Molecular mechanism for apoptosis and inhibition of reactive oxygen species induced through H2O2 were observed, concluding karanjin have medicinal and antioxidant properties.

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[1]
Kumar, G.; Ghosh, M.; Pandey, D.M. Method development for optimised green synthesis of gold nanoparticles from Millettia pinnata and their activity in non-small cell lung cancer cell lines. IET Nanobiotechnol., 2019, 13(6), 626-633.
[http://dx.doi.org/10.1049/iet-nbt.2018.5410] [PMID: 31432797]
[2]
Aggarwal, V.; Tuli, H.S.; Kaur, J.; Aggarwal, D.; Parashar, G.; Chaturvedi Parashar, N.; Kulkarni, S.; Kaur, G.; Sak, K.; Kumar, M.; Ahn, K.S. Garcinol exhibits anti-neoplastic effects by targeting diverse oncogenic factors in tumor cells. Biomedicines, 2020, 8(5), 103.
[http://dx.doi.org/10.3390/biomedicines8050103] [PMID: 32365899]
[3]
Kumar, G.; Gupta, R.; Sharan, S.; Roy, P.; Pandey, D.M. Anticancer activity of plant leaves extract collected from a tribal region of India. BioTech, 2019, 9(11), 1-16.
[4]
Eipeson, W.S.; Manjunatha, J.R.; Srinivas, P.; Kanya, T.S. Extraction and recovery of karanjin: A value addition to karanja (Pongamia pinnata) seed oil. Ind. Crops Prod., 2010, 32(2), 118-122.
[http://dx.doi.org/10.1016/j.indcrop.2010.03.011]
[5]
Roy, R.; Pal, D.; Sur, S.; Mandal, S.; Saha, P.; Panda, C.K. Pongapin and Karanjin, furanoflavanoids of PONGAMIA PINNATA, induce G2/M arrest and apoptosis in cervical cancer cells by differential reactive oxygen species modulation, DNA damage, and nuclear factor kappa-light-chain-enhancer of activated B cell signaling. Phytother. Res., 2019, 33(4), 1084-1094.
[http://dx.doi.org/10.1002/ptr.6302] [PMID: 30834631]
[6]
Tong, D.; Wang, X.; Liu, L.; Wen, T.; Chen, Q.; Huang, C. LAMC2 promotes EGFR cell membrane localization and acts as a novel biomarker for tyrosine kinase inhibitors (TKIs) sensitivity in lung cancer. Cancer Gene Ther., 2023, 1-15.
[http://dx.doi.org/10.1038/s41417-023-00654-7] [PMID: 37542131]
[7]
Guo, J.R.; Chen, Q.Q.; Lam, C.W.K.; Zhang, W. Effects of karanjin on cell cycle arrest and apoptosis in human A549, HepG2 and HL-60 cancer cells. Biol. Res., 2015, 48(1), 40.
[http://dx.doi.org/10.1186/s40659-015-0031-x] [PMID: 26209237]
[8]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[9]
Liu, G.; Pei, F.; Yang, F.; Li, L.; Amin, A.; Liu, S.; Buchan, J.; Cho, W. Role of autophagy and apoptosis in non-small-cell lung cancer. Int. J. Mol. Sci., 2017, 18(2), 367.
[http://dx.doi.org/10.3390/ijms18020367] [PMID: 28208579]
[10]
Nimesh, S.; Akram, M.; Chishti, M.A.; Ahmad, M.I.; Dhama, S.; Lal, M. Pongamia pinnata: An updated review on its phytochemistry, & pharmacological uses. Pharm. Pharmacol. Int. J., 2021, 9(5), 194-199.
[http://dx.doi.org/10.15406/ppij.2021.09.00344]
[11]
Kerr, J F R.; Wyllie, A.H.; Currie, A.R. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer, 1972, 26(4), 239-257.
[http://dx.doi.org/10.1038/bjc.1972.33] [PMID: 4561027]
[12]
Vogelstein, B.; Kinzler, K.W. p53 function and dysfunction. Cell, 1992, 70(4), 523-526.
[http://dx.doi.org/10.1016/0092-8674(92)90421-8] [PMID: 1505019]
[13]
Aubrey, B.J.; Kelly, G.L.; Janic, A.; Herold, M.J.; Strasser, A. How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ., 2018, 25(1), 104-113.
[http://dx.doi.org/10.1038/cdd.2017.169] [PMID: 29149101]
[14]
Inamura, K. Lung cancer: Understanding its molecular pathology and the 2015 WHO classification. Front. Oncol., 2017, 7, 193.
[http://dx.doi.org/10.3389/fonc.2017.00193] [PMID: 28894699]
[15]
Wang, R.A.; Li, Q.L.; Li, Z.S.; Zheng, P.J.; Zhang, H.Z.; Huang, X.F.; Chi, S.M.; Yang, A.G.; Cui, R. Apoptosis drives cancer cells proliferate and metastasize. J. Cell. Mol. Med., 2013, 17(1), 205-211.
[http://dx.doi.org/10.1111/j.1582-4934.2012.01663.x] [PMID: 23305095]
[16]
Jan, R.; Chaudhry, G.S. Understanding apoptosis and apoptotic pathways targeted cancer therapeutics. Adv. Pharm. Bull., 2019, 9(2), 205-218.
[http://dx.doi.org/10.15171/apb.2019.024] [PMID: 31380246]
[17]
Wachmann, K.; Pop, C.; van Raam, B.J.; Drag, M.; Mace, P.D.; Snipas, S.J.; Zmasek, C.; Schwarzenbacher, R.; Salvesen, G.S.; Riedl, S.J. Activation and specificity of human caspase-10. Biochemistry, 2010, 49(38), 8307-8315.
[http://dx.doi.org/10.1021/bi100968m] [PMID: 20795673]
[18]
Elmore, S. Apoptosis: a review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516.
[http://dx.doi.org/10.1080/01926230701320337] [PMID: 17562483]
[19]
Wagner, H.; Bladt, S. Plant drug analysis: A thin layer chromatography atlas; Springer Science & Business Media, 1996, pp. 195-245.
[http://dx.doi.org/10.1007/978-3-642-00574-9_8]
[20]
Rekha, M.J.; Bettadaiah, B.K.; Muthukumar, S.P.; Govindaraju, K. Synthesis, characterization and anti-inflammatory properties of karanjin (Pongamia pinnata seed) and its derivatives. Bioorg. Chem., 2021, 106, 104471.
[http://dx.doi.org/10.1016/j.bioorg.2020.104471] [PMID: 33257003]
[21]
Targett, N.M.; Kilcoyne, J.P.; Green, B. Vacuum liquid chromatography: An alternative to common chromatographic methods. J. Org. Chem., 1979, 44(26), 4962-4964.
[http://dx.doi.org/10.1021/jo00394a045]
[22]
Ahmed, H.; Moawad, A.; Owis, A.; AbouZid, S.; Ahmed, O. Flavonoids of Calligonum polygonoides and their cytotoxicity. Pharm. Biol., 2016, 54(10), 2119-2126.
[http://dx.doi.org/10.3109/13880209.2016.1146778] [PMID: 26922854]
[23]
Chen, L.; Jiang, J.; Cheng, C.; Yang, A.; He, Q.; Li, D.; Wang, Z. P53 dependent and independent apoptosis induced by lidamycin in human colorectal cancer cells. Cancer Biol. Ther., 2007, 6(6), 965-973.
[http://dx.doi.org/10.4161/cbt.6.6.4193] [PMID: 17534142]
[24]
Pandey, A.; Bajpai, A.K.; Kumar, A.; Pal, M.; Baboo, V.; Dwivedi, A. Isolation, identification, molecular and electronic structure, vibrational spectroscopic investigation, and anti-HIV-1 activity of karanjin using density functional theory. J. Theor. Chem., 2014, 2014(680987), 1-13.
[http://dx.doi.org/10.1155/2014/680987]
[25]
Singh, A.; Mukhopadhyay, K.; Ghosh Sachan, S. Biotransformation of eugenol to vanillin by a novel strain Bacillus safensis SMS1003. Biocatal. Biotransform., 2019, 37(4), 291-303.
[http://dx.doi.org/10.1080/10242422.2018.1544245]
[26]
Ginting, C.N.; Lister, I.N.E.; Girsang, E.; Widowati, W.; Yusepany, D.T.; Azizah, A.M.; Kusuma, H.S.W. Hepatotoxicity prevention in Acetaminophen-induced HepG2 cells by red betel (Piper crocatum Ruiz and Pav) extract from Indonesia via antioxidant, anti-inflammatory, and anti-necrotic. Heliyon, 2021, 7(1), e05620.
[http://dx.doi.org/10.1016/j.heliyon.2020.e05620] [PMID: 33474504]
[27]
Rio, D.C.; Ares, M., Jr; Hannon, G.J.; Nilsen, T.W. Purification of RNA using TRIzol (TRI reagent). Cold Spring Harb. Protoc., 2010, 2010(6), pdb.prot5439.
[http://dx.doi.org/10.1101/pdb.prot5439] [PMID: 20516177]
[28]
Skrypina, N.A.; Timofeeva, A.V.; Khaspekov, G.L.; Savochkina, L.P.; Beabealashvilli, R.S.H. Total RNA suitable for molecular biology analysis. J. Biotechnol., 2003, 105(1-2), 1-9.
[http://dx.doi.org/10.1016/S0168-1656(03)00140-8]
[29]
Mroczek, T.; Dymek, A.; Widelski, J.; Wojtanowski, K.K. The bioassay-guided fractionation and identification of potent acetylcholinesterase inhibitors from narcissus c.v. ‘Hawera’ using optimized vacuum liquid chromatography, high resolution mass spectrometry and bioautography. Metabolites, 2020, 10(10), 395.
[http://dx.doi.org/10.3390/metabo10100395] [PMID: 33020380]
[30]
Eroğlu, C.; Seçme, M.; Bağcı, G.; Dodurga, Y. Assessment of the anticancer mechanism of ferulic acid via cell cycle and apoptotic pathways in human prostate cancer cell lines. Tumour Biol., 2015, 36(12), 9437-9446.
[http://dx.doi.org/10.1007/s13277-015-3689-3] [PMID: 26124008]
[31]
Mottaghipisheh, J.; Iriti, M. Sephadex® LH-20, isolation, and purification of flavonoids from plant species: A comprehensive review. Molecules, 2020, 25(18), 4146.
[http://dx.doi.org/10.3390/molecules25184146] [PMID: 32927822]
[32]
Livak, K.J.; Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-∆ ∆ C(T)). Method. Methods, 2001, 25(4), 402-408.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[33]
Marima, R.; Hull, R.; Dlamini, Z.; Penny, C. Efavirenz induces DNA damage response pathway in lung cancer. Oncotarget, 2020, 11(41), 3737-3748.
[http://dx.doi.org/10.18632/oncotarget.27725] [PMID: 33110481]
[34]
Pajaniradje, S.; Mohankumar, K.; Pamidimukkala, R.; Subramanian, S.; Rajagopalan, R. Antiproliferative and apoptotic effects of Sesbania grandiflora leaves in human cancer cells. BioMed Res. Int., 2014, 2014, 1-11.
[http://dx.doi.org/10.1155/2014/474953] [PMID: 24949454]
[35]
Berman, H.M.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The protein data bank. Nucleic Acids Res., 2000, 28(1), 235-242.
[http://dx.doi.org/10.1093/nar/28.1.235] [PMID: 10592235]
[36]
Patel, H.M.; Shaikh, M.; Ahmad, I.; Lokwani, D.; Surana, S.J. BREED based de novo hybridization approach: Generating novel T790M/C797S-EGFR tyrosine kinase inhibitors to overcome the problem of mutation and resistance in non small cell lung cancer (NSCLC). J. Biomol. Struct. Dyn., 2021, 39(8), 2838-2856.
[http://dx.doi.org/10.1080/07391102.2020.1754918] [PMID: 32276580]
[37]
Shivanika, C.; Kumar, D.; Ragunathan, V.; Tiwari, P.; Sumitha, A. Molecular docking, validation, dynamics simulations, and pharmacokinetic prediction of natural compounds against the SARS-CoV-2 main-protease. J. Biomol. Struct. Dyn., 2022, 40(2), 585-611.
[http://dx.doi.org/10.1080/07391102.2020.1815584]
[38]
Kumar, B.K.; Faheem, N.; Sekhar, K.V.G.C.; Ojha, R.; Prajapati, V.K.; Pai, A.; Murugesan, S. Pharmacophore based virtual screening, molecular docking, molecular dynamics and MM-GBSA approach for identification of prospective SARS-CoV-2 inhibitor from natural product databases. J. Biomol. Struct. Dyn., 2022, 40(3), 1363-1386.
[http://dx.doi.org/10.1080/07391102.2020.1824814] [PMID: 32981461]
[39]
Subhani, S.; Jamil, K. Molecular docking of chemotherapeutic agents to CYP3A4 in non-small cell lung cancer. Biomed. Pharmacother., 2015, 73, 65-74.
[http://dx.doi.org/10.1016/j.biopha.2015.05.018] [PMID: 26211584]
[40]
Bergdorf, M.; Kim, E.T.; Rendleman, C.A.; Shaw, D.E. Desmond/GPU Performance as of November 2014. In: DE Shaw Research Technical Report DESRES/TR—2014-01; , 2014.
[41]
Burley, S.K.; Berman, H.M.; Kleywegt, G.J.; Markley, J.L.; Nakamura, H.; Velankar, S. Protein Data Bank (PDB): The Single Global Macromolecular Structure Archive. Methods Mol. Biol., 2017, 1, 607-627-641.
[http://dx.doi.org/10.1007/978]
[42]
Bao, X.; Zhang, Y.; Zhang, H.; Xia, L. Molecular mechanism of β-sitosterol and its derivatives in tumor progression. Front. Oncol., 2022, 12, 926975.
[http://dx.doi.org/10.3389/fonc.2022.926975] [PMID: 35756648]
[43]
Coates, J. Interpretation of infrared spectra, a practical approach. In: Encyclopedia of Analytical Chemistry; Meyers, R.A., Ed.; John Wiley & Sons Ltd: Chichester, 2000.
[44]
Harris, L.A.; Frick, P.L.; Garbett, S.P.; Hardeman, K.N.; Paudel, B.B.; Lopez, C.F.; Quaranta, V.; Tyson, D.R. An unbiased metric of antiproliferative drug effect in vitro. Nat. Methods, 2016, 13(6), 497-500.
[http://dx.doi.org/10.1038/nmeth.3852] [PMID: 27135974]
[45]
Wang, R.; Zhang, Q.; Peng, X.; Zhou, C.; Zhong, Y.; Chen, X.; Qiu, Y.; Jin, M.; Gong, M.; Kong, D. Stellettin B induces G1 arrest, apoptosis and autophagy in human non-small cell lung cancer A549 cells via blocking PI3K/Akt/mTOR pathway. Sci. Rep., 2016, 6(1), 27071.
[http://dx.doi.org/10.1038/srep27071] [PMID: 27243769]
[46]
Zorov, D.B.; Juhaszova, M.; Sollott, S.J. Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol. Rev., 2014, 94(3), 909-950.
[http://dx.doi.org/10.1152/physrev.00026.2013] [PMID: 24987008]
[47]
Fesik, S.W. Promoting apoptosis as a strategy for cancer drug discovery. Nat. Rev. Cancer, 2005, 5(11), 876-885.
[http://dx.doi.org/10.1038/nrc1736] [PMID: 16239906]
[48]
Vigneswara, V.; Ahmed, Z. The role of caspase-2 in regulating cell fate. Cells, 2020, 9(5), 1259.
[http://dx.doi.org/10.3390/cells9051259] [PMID: 32438737]
[49]
Ponder, K.G.; Boise, L.H. The prodomain of caspase-3 regulates its own removal and caspase activation. Cell Death Discov., 2019, 5(1), 56.
[http://dx.doi.org/10.1038/s41420-019-0142-1] [PMID: 30701088]
[50]
Leverson, J.D.; Zhang, H.; Chen, J.; Tahir, S.K.; Phillips, D.C.; Xue, J.; Nimmer, P.; Jin, S.; Smith, M.; Xiao, Y.; Kovar, P.; Tanaka, A.; Bruncko, M.; Sheppard, G.S.; Wang, L.; Gierke, S.; Kategaya, L.; Anderson, D.J.; Wong, C.; Eastham-Anderson, J.; Ludlam, M.J.C.; Sampath, D.; Fairbrother, W.J.; Wertz, I.; Rosenberg, S.H.; Tse, C.; Elmore, S.W.; Souers, A.J. Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Cell Death Dis., 2015, 6(1), e1590-e1590.
[http://dx.doi.org/10.1038/cddis.2014.561] [PMID: 25590800]
[51]
Román, M.; Baraibar, I.; López, I.; Nadal, E.; Rolfo, C.; Vicent, S.; Gil-Bazo, I. KRAS oncogene in non-small cell lung cancer: Clinical perspectives on the treatment of an old target. Mol. Cancer, 2018, 17(1), 33.
[http://dx.doi.org/10.1186/s12943-018-0789-x] [PMID: 29455666]
[52]
Jingwen, B.; Yaochen, L.; Guojun, Z. Cell cycle regulation and anticancer drug discovery. Cancer Biol. Med., 2017, 14(4), 348-362.
[http://dx.doi.org/10.20892/j.issn.2095-3941.2017.0033] [PMID: 29372101]
[53]
Plenchette, S.; Romagny, S.; Laurens, V.; Bettaieb, A. S-nitrosylation in TNF superfamily signaling pathway: Implication in cancer. Redox Biol., 2015, 6, 507-515.
[http://dx.doi.org/10.1016/j.redox.2015.08.019] [PMID: 26448396]
[54]
McArthur, K.; Whitehead, L.W.; Heddleston, J.M.; Li, L.; Padman, B.S.; Oorschot, V.; Geoghegan, N.D.; Chappaz, S.; Davidson, S.; San Chin, H.; Lane, R.M.; Dramicanin, M.; Saunders, T.L.; Sugiana, C.; Lessene, R.; Osellame, L.D.; Chew, T.L.; Dewson, G.; Lazarou, M.; Ramm, G.; Lessene, G.; Ryan, M.T.; Rogers, K.L.; van Delft, M.F.; Kile, B.T. BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis. Science, 2018, 359(6378), eaao6047.
[http://dx.doi.org/10.1126/science.aao6047] [PMID: 29472455]
[55]
Zhang, J.; Ming, C.; Zhang, W.; Okechukwu, P.N.; Morak-Młodawska, B.; Pluta, K.; Jeleń, M.; Akim, A.M.; Ang, K.P.; Ooi, K.K. 10H-3,6-Diazaphenothiazine induces G2/M phase cell cycle arrest and caspase-dependent apoptosis and inhibits cell invasion of A2780 ovarian carcinoma cells through the regulation of NF-κB and (BIRC6-XIAP) complexes. Drug Des. Devel. Ther., 2017, 11, 3045-3063.
[http://dx.doi.org/10.2147/DDDT.S144415] [PMID: 29123378]
[56]
Polosukhina, D.; Love, H.D.; Correa, H.; Su, Z.; Dahlman, K.B.; Pao, W.; Moses, H.L.; Arteaga, C.L.; Lovvorn, H.N., III; Zent, R.; Clark, P.E. Functional KRAS mutations and a potential role for PI3K/AKT activation in Wilms tumors. Mol. Oncol., 2017, 11(4), 405-421.
[http://dx.doi.org/10.1002/1878-0261.12044] [PMID: 28188683]
[57]
Hiraki, M.; Nishimura, J.; Takahashi, H.; Wu, X.; Takahashi, Y.; Miyo, M.; Nishida, N.; Uemura, M.; Hata, T.; Takemasa, I.; Mizushima, T.; Soh, J.W.; Doki, Y.; Mori, M.; Yamamoto, H. Concurrent targeting of KRAS and AKT by MiR-4689 is a novel treatment against mutant KRAS colorectal cancer. Mol. Ther. Nucleic Acids, 2015, 4(3), e231.
[http://dx.doi.org/10.1038/mtna.2015.5] [PMID: 25756961]
[58]
Unni, A.M.; Lockwood, W.W.; Zejnullahu, K.; Lee-Lin, S.Q.; Varmus, H. Evidence that synthetic lethality underlies the mutual exclusivity of oncogenic KRAS and EGFR mutations in lung adenocarcinoma. eLife, 2015, 4, e06907.
[http://dx.doi.org/10.7554/eLife.06907] [PMID: 26047463]
[59]
Martínez-Pérez, C.; Ward, C.; Turnbull, A.K.; Mullen, P.; Cook, G.; Meehan, J.; Jarman, E.J.; Thomson, P.I.T.; Campbell, C.J.; McPhail, D.; Harrison, D.J.; Langdon, S.P. Antitumour activity of the novel flavonoid Oncamex in preclinical breast cancer models. Br. J. Cancer, 2016, 114(8), 905-916.
[http://dx.doi.org/10.1038/bjc.2016.6] [PMID: 27031849]
[60]
Priness, I.; Maimon, O.; Ben-Gal, I. Evaluation of gene-expression clustering via mutual information distance measure. BMC Bioinformatics, 2007, 8(1), 111.
[http://dx.doi.org/10.1186/1471-2105-8-111] [PMID: 17397530]
[61]
Ganesan, R.; Jelakovic, S.; Mittl, P.R.E.; Caflisch, A.; Grütter, M.G. In silico identification and crystal structure validation of caspase-3 inhibitors without a P1 aspartic acid moiety. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun., 2011, 67(8), 842-850.
[http://dx.doi.org/10.1107/S1744309111018604] [PMID: 21821879]
[62]
Dwivedi, P.S.R.; Shastry, C.S. Anti-tumor potential and mode of action of karanjin against breast cancer; an in-silico approach. Arab. J. Chem., 2023, 16(6), 104778.
[http://dx.doi.org/10.1016/j.arabjc.2023.104778]
[63]
Ni, C.Z.; Li, C.; Wu, J.C.; Spada, A.P.; Ely, K.R. Conformational restrictions in the active site of unliganded human caspase-3. J. Mol. Recognit., 2003, 16(3), 121-124.
[http://dx.doi.org/10.1002/jmr.615] [PMID: 12833566]
[64]
Sulpizi, M.; Rothlisberger, U.; Carloni, P. Molecular dynamics studies of caspase-3. Biophys. J., 2003, 84(4), 2207-2215.
[http://dx.doi.org/10.1016/S0006-3495(03)75026-7] [PMID: 12668429]
[65]
Yao, L.; Swartz, P.; Hamilton, P.T.; Clark, A.C. Remodeling hydrogen bond interactions results in relaxed specificity of Caspase-3. Biosci. Rep., 2021, 41(1), BSR20203495.
[http://dx.doi.org/10.1042/BSR20203495] [PMID: 33448281]
[66]
Arnittali, M.; Rissanou, A.N.; Harmandaris, V. Structure of biomolecules through molecular dynamics simulations. Procedia Comput. Sci., 2019, 156, 69-78.
[http://dx.doi.org/10.1016/j.procs.2019.08.181]
[67]
Ahmadi, A.; Mohammadnejadi, E.; Razzaghi-Asl, N. Gefitinib derivatives and drug-resistance: A perspective from molecular dynamics simulations. Comput. Biol. Med., 2023, 163, 107204.
[http://dx.doi.org/10.1016/j.compbiomed.2023.107204] [PMID: 37421739]
[68]
Karnik, K.S.; Sarkate, A.P.; Lokwani, D.K.; Tiwari, S.V.; Azad, R.; Wakte, P.S. Molecular dynamic simulations based discovery and development of thiazolidin-4-one derivatives as EGFR inhibitors targeting resistance in non-small cell lung cancer (NSCLC). J. Biomol. Struct. Dyn., 2023, 41(10), 4696-4710.
[http://dx.doi.org/10.1080/07391102.2022.2071339] [PMID: 35532095]
[69]
Moradihaghgou, L.; Schneider, R.; Zanjani, B.M.; Harkinezhad, T. Comparative computational screening of natural-based partial agonists for PPARγ receptor. Med. Chem., 2023, 19(6), 594-618.
[http://dx.doi.org/10.2174/1573406419666230103142021] [PMID: 36597601]
[70]
Gnanaraj, C.; Sekar, M.; Fuloria, S.; Swain, S.S.; Gan, S.H.; Chidambaram, K.; Rani, N.N.I.M.; Balan, T.; Stephenie, S.; Lum, P.T.; Jeyabalan, S.; Begum, M.Y.; Chandramohan, V.; Thangavelu, L.; Subramaniyan, V.; Fuloria, N.K. In silico molecular docking analysis of karanjin against alzheimer’s and parkinson’s diseases as a potential natural lead molecule for new drug design, development and therapy. Molecules, 2022, 27(9), 2834.
[http://dx.doi.org/10.3390/molecules27092834] [PMID: 35566187]
[71]
Hospital, A.; Goñi, J.R.; Orozco, M.; Gelpí, J.L. Molecular dynamics simulations: Advances and applications. Adv. Appl. Bioinform. Chem., 2015, 8, 37-47.
[PMID: 26604800]
[72]
Binder, K.; Horbach, J.; Kob, W.; Paul, W.; Varnik, F. Molecular dynamics simulations. J. Phys. Condens. Matter, 2004, 16(5), S429-S453.
[http://dx.doi.org/10.1088/0953-8984/16/5/006]
[73]
Durrant, J.D.; McCammon, J.A. Molecular dynamics simulations and drug discovery. BMC Biol., 2011, 9(1), 71.
[http://dx.doi.org/10.1186/1741-7007-9-71] [PMID: 22035460]
[74]
Sargsyan, K.; Grauffel, C.; Lim, C. How molecular size impacts RMSD applications in molecular dynamics simulations. J. Chem. Theory Comput., 2017, 13(4), 1518-1524.
[http://dx.doi.org/10.1021/acs.jctc.7b00028] [PMID: 28267328]
[75]
da Fonseca, A.M.; Caluaco, B.J.; Madureira, J.M.C.; Cabongo, S.Q.; Gaieta, E.M.; Djata, F.; Colares, R.P.; Neto, M.M.; Fernandes, C.F.C.; Marinho, G.S.; dos Santos, H.S.; Marinho, E.S. Screening of potential inhibitors targeting the main protease structure of SARS-CoV-2 via molecular docking, and approach with molecular dynamics, RMSD, RMSF, H-bond, SASA and MMGBSA. Mol. Biotechnol., 2023, 1-15.
[http://dx.doi.org/10.1007/s12033-023-00831-x] [PMID: 37490200]

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