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Research Articles

Exploring the potential and identifying Withania somnifera alkaloids as novel dihydrofolate reductase (DHFR) inhibitors by the AlteQ method

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Pages 13963-13976 | Received 07 Oct 2022, Accepted 29 Jan 2023, Published online: 10 Feb 2023

References

  • Abkari, A., Chaabane, I., & Guidara, K. (2016). DFT (B3LYP/LanL2DZ and B3LYP/6311G+(d,p)) comparative vibrational spectroscopic analysis of organic–inorganic compound bis(4-acetylanilinium) tetrachlorocuprate(II). Physica E: Low-Dimensional Systems and Nanostructures. 81, 136–144.
  • Agarwal, P. K., Billeter, S. R., Rajagopalan, P. T., Benkovic, S. J., & Hammes-Schiffer, S. (2002). Network of coupled promoting motions in enzyme catalysis. Proceedings of the National Academy of Sciences of the United States of America, 99(5), 2794–2799. https://doi.org/10.1073/pnas.052005999
  • Appleton, D. R., Pearce, A. N., & Copp, B. R. (2010). Anti-tuberculosis natural products: Synthesis and biological evaluation of pyridoacridine alkaloids related to ascididemin. Tetrahedron, 66, 4977–4986.
  • Arora, K., & Brooks, C. L. (2009). Functionally important conformations of the met20 loop in dihydrofolate reductase are populated by rapid thermal fluctuations. Journal of the American Chemical Society, 131(15), 5642–5647. https://doi.org/10.1021/ja9000135
  • Au, S. W., Gover, S., Lam, V. M., & Adams, M. J. (2000). Human glucose-6-phosphate dehydrogenase: The crystal structure reveals a structural NADP+ molecule and provides insights into enzyme deficiency. Structure (London, England: 1993), 8(3), 293–303. https://doi.org/10.1016/S0969-2126(00)00104-0
  • Avilés, E., & Rodríguez, A. D. (2010). Monamphilectine A, a potent antimalarial β-lactam from marine sponge Hymeniacidon sp.: Isolation, structure, semisynthesis, and bioactivity. Organic Letters. 12, 5290–5293.
  • Bader, R. F. W. (1990). Atoms in molecules. A quantum theory. Oxford University Press.
  • Bhabha, G., Lee, J., Ekiert, D. C., Gam, J., Wilson, I. A., Dyson, H. J., Benkovic, S. J., & Wright, P. E. (2011). A dynamic knockout reveals that conformational fluctuations influence the chemical step of enzyme catalysis. Science (New York, N.Y.), 332(6026), 234–238. https://doi.org/10.1126/science.1198542
  • Blakley, R. L. (1984). Dihydrofolate reductase. In R. L. Blakley, & S. J. Benkovic (Eds.) Folates and pterines (pp. 191–253). Wiley.
  • Blakley, R. L. (1995). Eukaryotic dihydrofolate reductase. Advances in Enzymology and Related Areas of Molecular Biology, 70, 23–102. https://doi.org/10.1002/9780470123164.ch2
  • Boehr, D. D., McElheny, D., Dyson, H. J., & Wright, P. E. (2006). The dynamic energy landscape of dihydrofolate reductase catalysis. Science (New York, N.Y.), 313(5793), 1638–1642. https://doi.org/10.1126/science.1130258
  • Cameron, C. E., & Benkovic, S. J. (1997). Evidence for a functional role of the dynamics of glycine-121 of Escherichia coli dihydrofolate reductase obtained from kinetic analysis of a site-directed mutant. Biochemistry, 36(50), 15792–15800. https://doi.org/10.1021/bi9716231
  • Case, D. A., Betz, R. M., Cerutti, D. S., Cheatham, T. E. III., Darden, T. A., Duke, R. E., Giese, T. J., Gohlke, H., Goetz, A. W., Homeyer, N., Izadi, S., Janowski, P., Kaus, J., Kovalenko, A., Lee, T. S., LeGrand, S., Li, P., Lin, C., Luchko, T., … & Kollman, P. A. (2016). AMBER 2016. San Francisco: University of California.
  • Chawla, P., Kaur Gill, G. T. R., & Narang, R. K. (2021). An insight into synthetic strategies and recent developments of dihydrofolate reductase inhibitors. ChemistrySelect, 6, 12101–12145.
  • Chiarelli, L. R., Mori, G., Esposito, M., Orena, B. S., & Pasca, M. R. (2016). New and old hot drug targets in tuberculosis. Current Medicinal Chemistry, 23(33), 3813–3846. https://doi.org/10.2174/1389557516666160831164925
  • Darden, T., York, D., & Pedersen, L. (1993). Particle mesh Ewald: An N·log(N) method for Ewald sums in large systems. The Journal of Chemical Physics, 98, 10089–10092.
  • Desai, N. C., Trivedi, A. R., & Khedkar, V. M. (2016). Preparation, biological evaluation and molecular docking study of imidazolyl dihydropyrimidines as potential Mycobacterium tuberculosis dihydrofolate reductase inhibitors. Bioorganic & Medicinal Chemistry Letters, 26(16), 4030–4035. https://doi.org/10.1016/j.bmcl.2016.06.082
  • Ferenczy, G. G. (2015). Computation of drug-binding thermodynamics. In G. M. Keserü, & D. C. Swinney (Eds.) Thermodynamics and kinetics of drug binding (pp. 37–61). Wiley-VCH Verlag GmbH & Co. KGaA. https://doi.org/10.1002/9783527673025.ch3
  • Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Scalmani, G., Barone, V., Mennucci, B., Petersson, G. A., et al. (2010). Gaussian 09w, Gaussian 09, Rev, A.02. Gaussian Inc.
  • Gekko, K., Kunori, Y., Takeuchi, H., Ichihara, S., & Kodama, M. (1994). Point mutations at Glycine-121 of Escherichia coli dihydrofolate reductase: important roles of a flexible loop in the stability and function. Journal of Biochemistry, 116(1), 34–41. https://doi.org/10.1093/oxfordjournals.jbchem.a124499
  • Genheden, S., & Ryde, U. (2015). The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opinion on Drug Discovery, 10(5), 449–461. https://doi.org/10.1517/17460441.2015.1032936
  • Gohlke, H., Kiel, C., & Case, D. A. (2003). Insights into protein-protein binding by binding free energy calculation and free energy decomposition for the Ras-Raf and Ras-RalGDS complexes. Journal of Molecular Biology, 330(4), 891–913. https://doi.org/10.1016/s0022-2836(03)00610-7
  • Grishina, M. A., & Potemkin, V. A. (2019). Topological analysis of electron density in large biomolecular systems. Current Drug Discovery Technologies, 16(4), 437–448. https://doi.org/10.2174/1570163815666180821165330
  • Gurushankar, K., Rimac, H., Potemkin, V., & Grishina, M. (2021). Investigation of the newly characterized baimantuoluoamide a and baimantuoluoamide b alkaloids as potential cyclin-dependent kinase 4 (CDK4) inhibitors using molecular docking and molecular dynamics simulations. Journal of Molecular Structure, 1230, 129925.
  • Hajian, B., Scocchera, E., Keshipeddy, S., G-Dayanandan, N., Shoen, C., Krucinska, J., Reeve, S., Cynamon, M., Anderson, A. C., & Wright, D. L. (2016). Propargyl-linked antifolates are potent inhibitors of drug-sensitive and drug-resistant Mycobacterium tuberculosis. PloS One, 11(8), e0161740. https://doi.org/10.1371/journal.pone.0161740
  • Hong, W., Wang, Y., Chang, Z., Yang, Y., Pu, J., Sun, T., Kaur, S., Sacchettini, J. C., Jung, H., Wong, W. L., Yap, L. F., Ngeow, Y. F., Paterson, I. C., & Wang, H. (2015). The identification of novel Mycobacterium tuberculosis DHFR inhibitors and the investigation of their binding preferences by using molecular modelling. Scientific Reports, 5, 15328. https://doi.org/10.1038/srep15328
  • Hou, T., Wang, J., Li, Y., & Wang, W. (2011). Assessing the performance of the MM/PBSA and MM/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations. Journal of Chemical Information and Modeling, 51(1), 69–82.
  • https://clinicaltrials.gov/ct2/history/NCT05077813?V_1=View
  • https://www.who.int/news-room/fact-sheets/detail/tuberculosis
  • Isaka, M., Boonkhao, B., Rachtawee, P., & Auncharoen, P. (2007). A Xanthocillin-like alkaloid from the insect pathogenic fungus Cordyceps brunnearubra BCC 1395. Journal of Natural Products, 70(4), 656–658. https://doi.org/10.1021/np060509t
  • Islam, M. M., Pal, T. K., Paul, S., Uddin, M. N., Sheikh, M. C., Ashraful, M. A., & Hossen, J. (2022). Computational, Hirshfeld surface, and molecular docking analysis of 2-(((4-methoxyphenyl)imino)methyl)-4-nitrophenol: In-vitro anticancer, antimicrobial, anti-inflammatory, and antioxidant studies. Results in Chemistry, 4, 100331.
  • Jain, J., Narayanan, V., Chaturvedi, S., Pai, S., & Sunil, S. (2018). In vivo evaluation of Withania somnifera-based Indian traditional formulation (Amukkara Choornam), against chikungunya virus-induced morbidity and arthralgia. Journal of Evidence-Based Integrative Medicine, 23, 1–7. https://doi.org/10.1177/215658721875766
  • Karuppasamy, A., Krishnan, K. G., Velayutham Pillai, M. P., & Ramalingan, C. (2017). Synthesis, molecular structure and vibrational analysis of D-D-A based carbazole decorated phenothiazine-3-carbaldehyde: Experimental (FT-IR, UV and NMR) and density functional theory (DFT) calculations. Journal of Molecular Structure, 1128, 674–684. https://doi.org/10.1016/j.molstruc.2016.09.026
  • Kronenberger, T., Ferreira, G. M., de Souza, A. D. F., da Silva Santos, S., Poso, A., Ribeiro, J. A., Tavares, M. T., Pavan, F. R., Trossini, G. H. G., Dias, M. V. B., & Parise-Filho, R. (2020). Design, synthesis and biological activity of novel substituted 3-benzoic acid derivatives as MtDHFR inhibitors. Bioorganic & Medicinal Chemistry, 28(15), 115600. https://doi.org/10.1016/j.bmc.2020.115600
  • Kumar, A., Guardia, A., Colmenarejo, G., Pérez, E., Gonzalez, R. R., Torres, P., Calvo, D., Gómez, R. M., Ortega, F., Jiménez, E., Gabarro, R. C., Rullás, J., Ballell, L., & Sherman, D. R. (2015). A focused screen identifies antifolates with activity on Mycobacterium tuberculosis. ACS Infectious Diseases, 1(12), 604–614. https://doi.org/10.1021/acsinfecdis.5b00063
  • Kumar, A., Zhang, M., Zhu, L., Liao, R. P., Mutai, C., Hafsat, S., Sherman, D. R., & Wang, M. W. (2012). High-throughput screening and sensitized bacteria identify an M. tuberculosis dihydrofolate reductase inhibitor with whole cell activity. PLoS One. 7, e39961.
  • Lakshminarayanan, S., Jeyasingh, V., Murugesan, K., Selvapalam, N., & Dass, G. (2021). Molecular electrostatic potential (MEP) surface analysis of chemo sensors: An extra supporting hand for strength, selectivity & non-traditional interactions. Journal of Photochemistry and Photobiology, 6, 100022.
  • Lechartier, B., Rybniker, J., Zumla, A., & Cole, S. T. (2014). Tuberculosis drug discovery in the post-post-genomic era. EMBO Molecular Medicine, 6(2), 158–168. https://doi.org/10.1002/emmm.201201772
  • Machado, M. R., & Pantano, S. (2020). Split the charge difference in two! A rule of thumb for adding proper amounts of ions in MD simulations. Journal of Chemical Theory and Computation, 16, 1367–1372.
  • Maier, J. A., Martinez, C., Kasavajhala, K., Wickstrom, L., Hauser, K. E., & Simmerling, C. (2015). ff14SB: Improving the accuracy of protein side chain and backbone parameters from ff99SB. Journal of Chemical Theory and Computation, 11(8), 3696–3713. https://doi.org/10.1021/acs.jctc.5b00255
  • Malhotra, C. L., Mehta, V. L., Das, P. K., & Dhalla, N. S. (1965). Studies on Withania-ashwagandha, Kaul. V. The effect of total alkaloids (ashwagandholine) on the central nervous system. Indian Journal of Physiology and Pharmacology, 9(3), 127–136.
  • Mishra, S. K., Tripathi, G., Kishore, N., Singh, R. K., Singh, A., & Tiwari, V. K. (2017). Drug development against tuberculosis: Impact of alkaloids. European Journal of Medicinal Chemistry, 137, 504–544. https://doi.org/10.1016/j.ejmech.2017.06.005
  • Moon, A., Khan, D., Gajhbiye, P., & Jariya, M. (2017). In silico studies of inhibitors of dihydrofolate reductase and dihydropterate synthase of E. coli. International Journal of Pharmacy and Technology, 9, 28816–28829.
  • Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J. (2009). AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16), 2785–2791. https://doi.org/10.1002/jcc.21256
  • Nixon, M. R., Saionz, K. W., Koo, M. S., Szymonifka, M. J., Jung, H., Roberts, J. P., Nandakumar, M., Kumar, A., Liao, R., Rustad, T., Sacchettini, J. C., Rhee, K. Y., Freundlich, J. S., & Sherman, D. R. (2014). Folate pathway disruption leads to critical disruption of methionine derivatives in Mycobacterium tuberculosis. Chemistry & Biology, 21(7), 819–830. https://doi.org/10.1016/j.chembiol.2014.04.009
  • Ohmae, E., Ishimura, K., Iwakura, M., & Gekko, K. (1998). Effects of point mutations at the flexible loop alanine-145 of Escherichia coli dihydrofolate reductase on its stability and function. Journal of Biochemistry, 123(5), 839–846. https://doi.org/10.1093/oxfordjournals.jbchem.a022013
  • Pahal, S., Gupta, A., Choudhary, P., Chaudhary, A., & Singh, S. (2021). Network pharmacological evaluation of Withania somnifera bioactive phytochemicals for identifying novel potential inhibitors against neurodegenerative disorder. Journal of Biomolecular Structure and Dynamics, 40(21), 10887–10898. https://doi.org/10.1080/07391102.2021.195135
  • Palko, N., Grishina, M., & Potemkin, V. (2021). Electron density analysis of SARS-CoV-2 RNA-dependent RNA polymerase complexes. Molecules, 26, 3960. https://doi.org/10.3390/molecules26133960
  • Parashar, A., Shukla, A., Sharma, A., Behl, T., Goswami, D., & Mehta, V. (2021). Reckoning c-Glutamyl-S-allylcysteine as a potential main protease (MPRO) inhibitor of novel SARS-CoV-2 virus identified using docking and molecular dynamics simulation. Drug Development and Industrial Pharmacy, 47(5), 699–710. https://doi.org/10.1080/03639045.2021.1934857
  • Pettersen, E. F., Goddard, T. G., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004). UCSF Chimera-A visualization system for exploratory research and analysis. Journal of Computational Chemistry, 25(13), 1605–1612.
  • Potemkin, V. A., & Grishina, M. A. (2008). A new paradigm for pattern recognition of drugs. Journal of Computer-Aided Molecular Design, 22(6–7), 489–505. https://doi.org/10.1007/s10822-008-9203-x
  • Potemkin, V., Palko, N., & Grishina, M. (2019). Quantum theory of atoms in molecules for photovoltaics. Solar Energy, 190, 475–487. https://doi.org/10.1016/j.solener.2019.08.048
  • Rastelli, G., Rio, A. D., Degliesposti, G., & Sgobba, M. (2010). Fast and accurate predictions of binding free energies using MM-PBSA and MM-GBSA. Journal of Computational Chemistry, 31(4), 797–810.
  • Ribeiro, J. A., Chavez-Pacheco, S. M., Stephani de Oliveira, G. B., Santos Silva, G. D., João Henrique Pimenta Giudice, J. H., Libreros-Zúñiga, G. A., & Dias, M. V. B. (2019). Crystal structures of the closed form of Mycobacterium tuberculosis dihydrofolate reductase in complex with dihydrofolate and antifolates. Acta Crystallographica. Section D, Structural Biology, 75(Pt 7), 682–693.
  • Rimac, H., Grishina, M. A., & Potemkin, V. A. (2020). Electron density analysis of CDK complexes using the AlteQ method. Future Medicinal Chemistry, 12(15), 1387–1397. https://doi.org/10.4155/fmc-2020-0076
  • Rod, T. H., Radkiewicz, J. L., & Brooks, C. L. (2003). Correlated motion and the effect of distal mutations in dihydrofolate reductase. Proceedings of the National Academy of Sciences of the United States of America, 100(12), 6980–6985. https://doi.org/10.1073/pnas.1230801100
  • Roe, D. R., & Cheatham, T. E. (2013). PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data. Journal of Chemical Theory and Computation, 9(7), 3084–3095. https://doi.org/10.1021/ct400341p
  • Ryckaert, J. P., Ciccotti, G., & Berendsen, H. J. C. (1977). Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. Journal of Computational Physics, 23, 327–341.
  • Šali, A., & Blundell, T. L. (1993). Comparative protein modelling by satisfaction of spatial restraints. Journal of Molecular Biology, 234(3), 779–815. https://doi.org/10.1006/jmbi.1993.1626
  • Salmina, E., Grishina, M. A., & Potemkin, V. A. (2013). An approximation of the Cioslowski-Mixon bond order indexes using the AlteQ approach. Journal of Computer-Aided Molecular Design, 27(9), 793–805. https://doi.org/10.1007/s10822-013-9677-z
  • Sawaya, M. R., & Kraut, J. (1997). Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: Crystallographic evidence. Biochemistry, 36(3), 586–603. https://doi.org/10.1021/bi962337c
  • Schnell, J. R., Dyson, H. J., & Wright, P. E. (2004). Structure, dynamics, and catalytic function of dihydrofolate reductase. Annual Review of Biophysics and Biomolecular Structure, 33, 119–140. https://doi.org/10.1146/annurev.biophys.33.110502.133613
  • Sharma, K., Tanwar, O., Deora, G. S., Ali, S., Alam, M., Zaman, M., Krishna, V. S., Sriram, D., & Akhter, M. (2019). Expansion of a novel lead targeting M. tuberculosis DHFR as antitubercular agents. Bioorganic & Medicinal Chemistry, 27(7), 1421–1429. https://doi.org/10.1016/j.bmc.2019.02.053
  • Shelke, R. U., Degani, M. S., Raju, A., Ray, M. K., & Rajan, M. G. (2016). Fragment discovery for the design of nitrogen heterocycles as Mycobacterium tuberculosis dihydrofolate reductase inhibitors. Archiv Der Pharmazie, 349(8), 602–613. https://doi.org/10.1002/ardp.201600066
  • Sittikornpaiboon, P., Toochinda, P., & Lawtrakul, L. (2017). Structural and dynamics perspectives on the binding of substrate and inhibitors in Mycobacterium tuberculosis DHFR. Scientia Pharmaceutica, 85(3), 31. https://doi.org/10.3390/scipharm85030031
  • Tawari, N. R., Bag, S., Raju, A., Lele, A. C., Bairwa, R., Ray, M. K., Rajan, M. G. R., Nawale, L. U., Sarkar, D., & Degani, M. S. (2015). Rational drug design, synthesis and biological evaluation of dihydrofolate reductase inhibitors as antituberculosis agents. Future Medicinal Chemistry, 7(8), 979–988.
  • Tiberi, S., Muñoz-Torrico, M., Duarte, R., Dalcolmo, M., D'Ambrosio, L., & Migliori, G.-B. (2018). New drugs and perspectives for new anti-tuberculosis regimens. Pulmonology, 24(2), 86–98.
  • Trott, O., & Olson, A. J. (2009). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry, 29, 455–461.
  • Vetvicka, V., & Vetvickova, J. (2011). Immune enhancing effects of WB365, a novel combination of Ashwagandha (Withania somnifera) and Maitake (Grifola frondosa) extracts. North American Journal of Medical Sciences, 3(7), 320–324.
  • Wang, L., Goodey, N. M., Benkovic, S. J., & Kohen, A. (2006a). Coordinated effects of distal mutations on environmentally coupled tunneling in dihydrofolate reductase. Proceedings of the National Academy of Sciences of the United States of America, 103(43), 15753–15758. https://doi.org/10.1073/pnas.0606976103
  • Wang, J., Wang, W., Kollman, P. A., & Case, D. A. (2006b). Automatic atom type and bond type perception in molecular mechanical calculations. Journal of Molecular Graphics & Modelling, 25(2), 247–260.
  • Yamada, K., Hung, P., Park, T. K., Park, P. J., & Lim, B. O. (2011). A comparison of the immunostimulatory effects of the medicinal herbs Echinacea, Ashwagandha and Brahmi. Journal of Ethnopharmacology, 137(1), 231–235. https://doi.org/10.1016/j.jep.2011.05.017
  • Yan, Y., Li, X., Zhang, C., Lv, L., Gao, B., & Li, M. (2021). Research progress on antibacterial activities and mechanisms of natural alkaloids: A review. Antibiotics, 10, 318.
  • Ziauddin, M., Phansalkar, N., Patki, P., Diwanay, S., & Patwardhan, B. (1996). Studies on the immunomodulatory effects of Ashwagandha. Journal of Ethnopharmacology, 50(2), 69–76. https://doi.org/10.1016/0378-8741(95)01318-0

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