Computer-aided synthesis of dapsone-phytochemical conjugates against dapsone-resistant Mycobacterium leprae.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 04 2020
22 04 2020
Historique:
received:
28
01
2019
accepted:
23
01
2020
entrez:
24
4
2020
pubmed:
24
4
2020
medline:
25
11
2020
Statut:
epublish
Résumé
Leprosy continues to be the belligerent public health hazard for the causation of high disability and eventual morbidity cases with stable prevalence rates, even with treatment by the on-going multidrug therapy (MDT). Today, dapsone (DDS) resistance has led to fear of leprosy in more unfortunate people of certain developing countries. Herein, DDS was chemically conjugated with five phytochemicals independently as dapsone-phytochemical conjugates (DPCs) based on azo-coupling reaction. Possible biological activities were verified with computational chemistry and quantum mechanics by molecular dynamics simulation program before chemical synthesis and spectral characterizations viz., proton-HNMR, FTIR, UV and LC-MS. The in vivo antileprosy activity was monitored using the 'mouse-foot-pad propagation method', with WHO recommended concentration 0.01% mg/kg each DPC for 12 weeks, and the host-toxicity testing of the active DPC4 was seen in cultured-human-lymphocytes in vitro. One-log bacilli cells in DDS-resistant infected mice footpads decreased by the DPC4, and no bacilli were found in the DDS-sensitive mice hind pads. Additionally, the in vitro host toxicity study also confirmed that the DCP4 up to 5,000 mg/L level was safety for oral administration, since a minor number of dead cells were found in red color under a fluorescent microscope. Several advanced bioinformatics tools could help locate the potential chemical entity, thereby reducing the time and resources required for in vitro and in vitro tests. DPC4 could be used in place of DDS in MDT, evidenced from in vivo antileprosy activity and in vitro host toxicity study.
Identifiants
pubmed: 32322091
doi: 10.1038/s41598-020-63913-9
pii: 10.1038/s41598-020-63913-9
pmc: PMC7176699
doi:
Substances chimiques
Leprostatic Agents
0
Phytochemicals
0
Dapsone
8W5C518302
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6839Références
Swain, S. S. et al. Molecular docking and simulation study for synthesis of alternative dapsone derivative as a newer anti-leprosy drug in multidrug therapy. J. Cellular. Biochem. 119, 9838–52 (2018).
doi: 10.1002/jcb.27304
Chaitanya, S. V., Das, M., Bhat, P. & Ebenezer, M. Computational modelling of dapsone interaction with dihydropteroate synthase in Mycobacterium leprae; insights into molecular basis of dapsone resistance in leprosy. J. Cell. Biochem. 116, 2293–2303 (2015).
doi: 10.1002/jcb.25180
World Health Organization. Weekly Epidemiological Record 92, 501–20 (2016).
Head, M. G. et al. Research investments in global health: A systematic analysis of UK infectious disease research funding and global health metrics, 1997-2013. EBioMedicine 3, 180–90 (2015).
doi: 10.1016/j.ebiom.2015.12.016
Saunderson, P. R. Drug-resistant Mycobacterium leprae. Clin. Dermatol. 34, 79–81 (2016).
doi: 10.1016/j.clindermatol.2015.10.019
Gupta, U. D., Katoch, K. & Katoch, V. M. Study of rifampicin resistance and comparison of dapsone resistance of M. leprae in pre- and post-MDT era. Indian J Lepr. 81, 131–34 (2009).
pubmed: 20509341
Teschke, R. & Danan, G. Drug induced liver injury: alternative causes in case series as confounding variables. Br. J. Clin. Pharmacol. 84, 1467–77 (2018).
doi: 10.1111/bcp.13593
Oliveira, F. R., Pessoa, M. C., Albuquerque, R. F. V., Schalcher, T. R. & Monteiro, M. C. Clinical applications and methemoglobinemia induced by dapsone. J. Braz. Chem. Soc. 25, 1770–1779 (2014).
Swain, S. S., Paidesetty, S. K. & Padhy, R. N. Development of antibacterial conjugates using sulfamethoxazole with monocyclic terpenes: A systematic medicinal chemistry based computational approach. Comput. Method. Program. Biomed. 140, 185–94 (2017).
doi: 10.1016/j.cmpb.2016.12.013
Zhu, Y. I. & Stiller, M. J. Dapsone and sulfones in dermatology: overview and update. J. Am. Acad. Dermatol. 45, 420–34 (2001).
doi: 10.1067/mjd.2001.114733
Nakata, N., Kai, M. & Makino, M. Mutation analysis of the Mycobacterium leprae folP1 gene and dapsone resistance. Antimicrob. Agent. Chemother. 55, 762–66 (2011).
doi: 10.1128/AAC.01212-10
Kai, M. et al. Diaminodiphenyl sulfone resistance of Mycobacterium leprae due to mutations in the dihydropteroate synthase gene. FEMS Microbiol. Lett. 177, 231–35 (1999).
doi: 10.1111/j.1574-6968.1999.tb13737.x
Lavania, M. et al. Emergence of primary drug resistance to rifampicin in Mycobacterium leprae strains from leprosy patients in India. Clin. Microbiol. Infect. 21, 85–6 (2015).
doi: 10.1016/j.cmi.2015.08.004
Yu, M. et al. Rifampicin-resistant Mycobacterium leprae in an elderly leprosy patient in the people’s Republic of China. Clin. Interv. Aging. 8, 1097–99 (2013).
pubmed: 23986632
pmcid: 3754489
Hammoudeh, D. I., Zhao, Y., White, S. W. & Lee, R. E. Replacing sulfa drugs with novel DHPS inhibitors. Future Med. Chem. 5, 1331–40 (2013).
doi: 10.4155/fmc.13.97
Baca, A. M., Sirawaraporn, R., Turley, S., Sirawaraporn, W. & Hol, W. G. J. Crystal structure of Mycobacterium tuberculosis 7, 8-dihydropteroate synthase in complex with pterin monophosphate: new insight into the enzymatic mechanism and sulfadrug action. J. Mol. Biol. 302, 1193–1212 (2000).
doi: 10.1006/jmbi.2000.4094
Mondal, M., Chakrabarti, J. & Ghosh, M. Molecular dynamics simulations on interaction between between bacterial proteins: Implication on pathogenic activities. Proteins 86, 370–78 (2018).
doi: 10.1002/prot.25446
Wang, C., Greene, D., Xiao, L., Qi, R. & Luo, R. Recent developments and applications of the MM/PBSA method. Front. Mol. Biosci. 4, 87, https://doi.org/10.3389/fmolb.2017.00087 (2018).
doi: 10.3389/fmolb.2017.00087
pubmed: 29367919
pmcid: 5768160
Dehury, B., Behera, S. K. & Mahapatra, N. Structural dynamics of casein kinase I (CKI) from malarial parasite Plasmodium falciparum (Isolate 3D7): Insights from theoretical modelling and molecular simulations. J. Mol. Graph. Model. 71, 154–66 (2017).
doi: 10.1016/j.jmgm.2016.11.012
Das, M., Chaitanya, S. V., Kanmani, K., Rajan, L. & Ebenezer, M. Genomic diversity in Mycobacterium leprae isolates from leprosy cases in South India. Infect. Genet Evol. 45, 285–89 (2016).
doi: 10.1016/j.meegid.2016.09.014
Williams, D. L. & Gillis, T. P. Drug-resistant leprosy: monitoring and current status. Lep. Rev. 83, 269–81 (2012).
Patnaik, R. & Padhy, R. N. Cellular and nuclear toxicity of HgCl2 to in vitro grown lymphocytes from human umbilical cord blood. PNAS India Sec. B Biol. Sci. 85, 821–30 (2015).
Gillis, D. L. & Williams, T. P. Drug-resistant leprosy: Monitoring and current status. Lep. Rev. 83, 269–81 (2012).
Rao, P. N. Recent advances in the control programs and therapy of leprosy. Indian J. Dermatol. Venereol. Leprol. 70, 269–76 (2004).
pubmed: 17642635
Makarov, V. et al. Synthesis and antileprosy activity of some dialkyldithiocarbamates. J. Antimicrob. Chemother. 57, 1134–38 (2006).
doi: 10.1093/jac/dkl095
Naqvi, A. A. T., Mohammad, T., Hasan, G. M. & Hassan, M. I. Advancements in docking and molecular dynamics simulations towards ligand-receptor interactions and structure-function relationships. Curr Top Med Chem. 18, 1755–68 (2018).
doi: 10.2174/1568026618666181025114157
Shahbaaz, M., Nkaule, A. & Christoffels, A. Designing novel possible kinase inhibitor derivatives as therapeutics against Mycobacterium tuberculosis: An in silico study. Sci Rep. 9, 4405, https://doi.org/10.1038/s41598-019-40621-7 (2019).
doi: 10.1038/s41598-019-40621-7
pubmed: 30867456
pmcid: 6416319
Pandey, B., Grover, S., Kaur, J. & Grover, A. Analysis of mutations leading to para-amino salicylic acid resistance in Mycobacterium tuberculosis. Sci Rep. 9, 13617, https://doi.org/10.1038/s41598-019-48940-5 (2019).
doi: 10.1038/s41598-019-48940-5
pubmed: 31541138
pmcid: 6754364
Lombard, M. C., N’Da, D. D., Breytenbach, J. C., Smith, P. J. & Lategan, C. A. Artemisinin-quinoline hybrid-dimers: synthesis and in vitro antiplasmodial activity. Bioorgan. Med. Chem. Let. 20, 6975–77 (2010).
doi: 10.1016/j.bmcl.2010.09.130
Bauer, A. & Brönstrup, M. Industrial natural product chemistry for drug discovery and development. Nat Prod Rep. 31, 35–60 (2014).
doi: 10.1039/C3NP70058E
Atanasov, A. G. et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol Adv. 33, 1582–1614 (2015).
doi: 10.1016/j.biotechadv.2015.08.001
Verdonk, M. L., Ludlow, R. F., Giangreco, I. & Rathi, P. C. Protein-ligand informatics force field (PLIff): Toward a fully knowledge driven “Force Field” for biomolecular interactions. J. Med. Chem. 59, 6891–6902 (2016).
doi: 10.1021/acs.jmedchem.6b00716
Swain, S. S., Paidesetty, S. K. & Padhy, R. N. Synthesis of novel thymol derivatives against MRSA and ESBL producing pathogenic bacteria. Nat Prod Res 33, 3181–89 (2019).
doi: 10.1080/14786419.2018.1474465
Fang, J. et al. Inhibition of acetylcholinesterase by two genistein derivatives: kinetic analysis, molecular docking and molecular dynamics simulation. Acta Pharm Sin B. 6, 430–37 (2014).
doi: 10.1016/j.apsb.2014.10.002
Lambert, J. M. & Berkenblit, A. Antibody-drug conjugates for cancer treatment. Annu. Rev. Med. 6, 191–207 (2018).
doi: 10.1146/annurev-med-061516-121357
Kuppusamy, P. et al. Nutraceuticals as potential therapeutic agents for colon cancer: a review. Acta. Pharm. Sin B. 4, 173–81 (2014).
doi: 10.1016/j.apsb.2014.04.002
Muregi, F. W. & Ishih, A. Next-generation antimalarial drugs: hybrid molecules as a new strategy in drug design. Drug Develop Res. 71, 20–32 (2010).
Wei, B. et al. Discovery of peptidomimetic antibody-drug conjugate linkers with enhanced protease specificity. J. Med. Chem. 61, 989–1000 (2018).
doi: 10.1021/acs.jmedchem.7b01430