438
Views
25
CrossRef citations to date
0
Altmetric
Original Research

In silico Design and Synthesis of Tetrahydropyrimidinones and Tetrahydropyrimidinethiones as Potential Thymidylate Kinase Inhibitors Exerting Anti-TB Activity Against Mycobacterium tuberculosis

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, , ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon, , ORCID Icon & ORCID Icon show all
Pages 1027-1039 | Published online: 09 Mar 2020

References

  • WHO. Global tuberculosis report 2018, Geneva; 2018 Availabe from: https://www.who.int/tb/publications/global_report/en/. Accessed 124, 2019.
  • ShruthiT, EswaranS, ShivarudraiahP, NarayananS, SubramanianS. Synthesis, antituberculosis studies and biological evaluation of new quinoline derivatives carrying 1, 2, 4-oxadiazole moiety. Bioorg Med Chem Lett. 2019;29(1):97–102. doi:10.1016/j.bmcl.2018.11.00230448235
  • MarcosAE. The global situation of MDR-TB. Tuberculosis. 2003;83:44–51. doi:10.1016/S1472-9792(02)00058-612758188
  • CamineroJA, SotgiuG, ZumlaA, MiglioriGB. Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis. Lancet Infect Dis. 2010;10(9):621–629. doi:10.1016/S1473-3099(10)70139-020797644
  • HuY, XuL, HeYL, et al. Prevalence and molecular characterization of second-line drugs resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Southwest of China. Biomed Res Int. 2017;2017:4563826. doi:10.1155/2017/456382628798931
  • ParidaSK, Axelsson-RobertsonR, RaoMV, et al. Totally drug-resistant tuberculosis and adjunct therapies. J Intern Med. 2015;277(4):388–405. doi:10.1111/joim.2015.277.issue-424809736
  • CoxE, LaessigK. FDA approval of bedaquiline — the benefit–risk balance for drug-resistant tuberculosis. N Engl J Med. 2014;371(8):689–691. doi:10.1056/NEJMp131438525140952
  • Barry IiiCE. Timing is everything for compassionate use of delamanid. Nat Med. 2015;21(3):211. doi:10.1038/nm.382325742452
  • FamiliarO, Munier‐LehmannH, NegriA, et al. Exploring acyclic nucleoside analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase. ChemMedChem. 2008;3(7):1083–1093. doi:10.1002/cmdc.v3:718418833
  • VanheusdenV, Munier-LehmannH, PochetS, HerdewijnP, Van CalenberghS. Synthesis and evaluation of thymidine-5′-O-monophosphate analogues as inhibitors of Mycobacterium tuberculosis thymidylate kinase. Bioorg Med Chem Lett. 2002;12(19):2695–2698. doi:10.1016/S0960-894X(02)00551-612217356
  • AlexandrovaLA, ChekhovVO, ShmalenyukER, KochetkovSN, El-AsrarRA, HerdewijnP. Synthesis and evaluation of C-5 modified 2’-deoxyuridine monophosphates as inhibitors of M. tuberculosis thymidylate synthase. Bioorg Med Chem. 2015;23(22):7131–7137. doi:10.1016/j.bmc.2015.09.05326482569
  • ShmalenyukER, ChernousovaLN, KarpenkoIL, et al. Inhibition of Mycobacterium tuberculosis strains H37Rv and MDR MS-115 by a new set of C5 modified pyrimidine nucleosides. Bioorg Med Chem. 2013;21(17):4874–4884. doi:10.1016/j.bmc.2013.07.00323891229
  • TotiKS, VerbekeF, RisseeuwMD, FrecerV, Munier-LehmannH, Van CalenberghS. Synthesis and evaluation of 5′-modified thymidines and 5-hydroxymethyl-2′-deoxyuridines as Mycobacterium tuberculosis thymidylate kinase inhibitors. Bioorg Med Chem. 2013;21(1):257–268. doi:10.1016/j.bmc.2012.10.01823199481
  • Van PoeckeS, Munier-LehmannH, HelynckO, FroeyenM, Van CalenberghS. Synthesis and inhibitory activity of thymidine analogues targeting Mycobacterium tuberculosis thymidine monophosphate kinase. Bioorg Med Chem. 2011;19(24):7603–7611. doi:10.1016/j.bmc.2011.10.02122061826
  • FamiliarO, Munier-LehmannH, AínsaJA, CamarasaM-J, Pérez-PérezM-J. Design, synthesis and inhibitory activity against Mycobacterium tuberculosis thymidine monophosphate kinase of acyclic nucleoside analogues with a distal imidazoquinolinone. Eur J Med Chem. 2010;45(12):5910–5918. doi:10.1016/j.ejmech.2010.09.05620951473
  • FioravantiE, AdamV, Munier-LehmannH, BourgeoisD. The crystal structure of Mycobacterium tuberculosis thymidylate kinase in complex with 3‘-azidodeoxythymidine monophosphate suggests a mechanism for competitive inhibition. Biochemistry. 2005;44(1):130–137. doi:10.1021/bi048416315628853
  • PochetS, DugueL, LabesseG, DelepierreM, Munier-LehmannH. Comparative study of purine and pyrimidine nucleoside analogues acting on the thymidylate kinases of Mycobacterium tuberculosis and of humans. Chembiochem. 2003;4(8):742–747. doi:10.1002/cbic.20030060812898625
  • SongL, MerceronR, GraciaB, et al. Structure guided lead generation toward nonchiral M. tuberculosis thymidylate kinase inhibitors. J Med Chem. 2018;61(7):2753–2775. doi:10.1021/acs.jmedchem.7b0157029510037
  • KawatkarSP, KeatingTA, OlivierNB, et al. Antibacterial inhibitors of gram-positive thymidylate kinase: structure–activity relationships and chiral preference of a new hydrophobic binding region. J Med Chem. 2014;57(11):4584–4597. doi:10.1021/jm500463c24828090
  • Martinez-BotellaG, BreenJN, DuffyJE, et al. Discovery of selective and potent inhibitors of gram-positive bacterial thymidylate kinase (TMK). J Med Chem. 2012;55(22):10010–10021. doi:10.1021/jm301180623043329
  • GasseC, DouguetD, HuteauV, MarchalG, Munier-LehmannH, PochetS. Substituted benzyl-pyrimidines targeting thymidine monophosphate kinase of Mycobacterium tuberculosis: synthesis and in vitro anti-mycobacterial activity. Bioorg Med Chem. 2008;16(11):6075–6085. doi:10.1016/j.bmc.2008.04.04518467107
  • NaikM, RaichurkarA, BandodkarBS, et al. Structure guided lead generation for M. tuberculosis thymidylate kinase (Mtb TMK): discovery of 3-cyanopyridone and 1,6-naphthyridin-2-one as potent inhibitors. J Med Chem. 2015;58(2):753–766. doi:10.1021/jm501294725486447
  • Hoffmann-H-H, KunzA, SimonVA, PaleseP, ShawML. Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis. Proc Natl Acad Sci U S A. 2011;108(14):5777–5782, S5777/5771-S5777/5774. doi:10.1073/pnas.1101143108
  • PrachayasittikulS, PingaewR, WorachartcheewanA, et al. Roles of pyridine and pyrimidine derivatives as privileged scaffolds in anticancer agents. Mini Rev Med Chem. 2017;17(10):869–901. doi:10.2174/138955751666616092312580127670581
  • KarnailSA, BrianNS, StevenEU, et al. Dihydropyrimidine calcium channel blockers. 3. 3-Carbamoyl-4-aryl-1,2,3,4-tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effective antihypertensive agents. J Med Chem. 1991;34(2):806–811. doi:10.1021/jm00106a0481995904
  • JaukB, PernatT, KappeCO. Design and synthesis of a conformationally rigid mimic of the dihydropyrimidine calcium channel modulator SQ 32,926. Molecules. 2000;5:227–239. doi:10.3390/50300227
  • VenugopalaKN, NayakSK, PillayM, PrasannaR, CoovadiaYM, OdhavB. Synthesis and antitubercular activity of 2-(substituted phenyl/benzyl-amino)-6-(4-chlorophenyl)-5-(methoxycarbonyl)-4-methyl-3,6-dihydropyrimidin-1-ium chlorides. Chem Biol Drug Des. 2013;81(2):219–227. doi:10.1111/cbdd.1206523150983
  • VenugopalaKN, Dharma RaoGB, BhandaryS, et al. Design, synthesis, and characterization of (1-(4-aryl)-1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates against Mycobacterium tuberculosis. Drug Des Dev Ther. 2016;10:2681–2690. doi:10.2147/DDDT
  • WaelAES, IbrahimFN, AdelAH, AbdelR. C-Furyl glycosides, II: synthesis and antimicrobial evaluation of C-furyl glycosides bearing pyrazolines, isoxazolines, and 5,6-dihydropyrimidine-2(1H)-thiones. Monatsh Chem. 2009;140:365–370. doi:10.1007/s00706-008-0033-2
  • ShahTB, GupteA, PatelMR, ChaudhariVS, PatelH, PatelVC. Synthesis and in vitro study of biological activity of heterocyclic N-Mannich bases of 3,4-dihydropyrimidine-2(1H)-thiones. Indian J Chem. 2010;49 B(05):578–586.
  • SushilkumarSB, DevanandBS. Synthesis and anti-inflammatory activity of some 2-amino-6-(4-substituted aryl)-4-(4-substituted phenyl)-1,6-dihydropyrimidine-5-yl-acetic acid derivatives. Acta Pharm. 2003;53:223–229.14769245
  • NofalZM, FahmyHH, ZareaES, El-ErakyW. Synthesis of new pyrimidine derivatives with evaluation of their anti-inflammatory and analgesic activities. Acta Pol Pharm. 2011;68(4):507–517.21796933
  • KeshabMB, NancySY, PromiseME, et al. Anti-diabetic activity of dihydropyrimidine scaffolds and structural insight by single crystal X-ray studies. Med Chem. 2019.
  • RajanarendarE, ReddyMN, MurthyKR, et al. Synthesis, antimicrobial, and mosquito larvicidal activity of 1-aryl-4-methyl-3,6-bis-(5-methylisoxazol-3-yl)-2-thioxo-2,3,6,10b-tetrahydro-1H-pyrimido[5,4-c]quinolin-5-ones. Bioorg Med Chem Lett. 2010;20(20):6052–6055. doi:10.1016/j.bmcl.2010.08.06020813527
  • VenugopalaKN, GleiserRM, ChalannavarRK, OdhavB. Antimosquito properties of 2-substituted phenyl/benzylamino-6-(4-chlorophenyl)-5-methoxycarbonyl-4-methyl-3,6-dihydropyrimidinium chlorides against Anopheles arabiensis. Med Chem. 2014;10(2):211–219. doi:10.2174/15734064100214013116494524506684
  • BairagiKM, VenugopalaKN, MondalPK, et al. Larvicidal study of tetrahydropyrimidine scaffolds against Anopheles arabiensis and structural insight by single crystal X-ray studies. Chem Biol Drug Des. 2018;92(6):1924–1932. doi:10.1111/cbdd.2018.92.issue-629923688
  • KhedrMA, PillayM, ChandrashekharappaS, et al. Molecular modeling studies and anti-TB activity of trisubstituted indolizine analogues; molecular docking and dynamic inputs. J Biomol Struct Dyn. 2018;36(8):2163–2178. doi:10.1080/07391102.2017.134532528657441
  • VenugopalaKN, ChandrashekharappaS, PillayM, et al. Synthesis and structural elucidation of novel benzothiazole derivatives as anti-tubercular agents: in-silico screening for possible target identification. Med Chem. 2019;15(3):311–326. doi:10.2174/157340641466618070312181529968540
  • VenugopalaKN, SandeepC, PillayM, et al. Computational, crystallographic studies, cytotoxicity and anti-tubercular activity of substituted 7-methoxy-indolizine analogues. PLoS One. 2019;14(6):PONE-D-19-08053R1.
  • VenugopalaKN, TratratC, PillayM, et al. Anti-tubercular activity of substituted 7-methyl and 7-formylindolizines and in silico study for prospective molecular target identification. Antibiotics. 2019;8(247):1–16. doi:10.3390/antibiotics8040247
  • NayakSK, VenugopalaKN, ChopraD, RowTNG. Insights into conformational and packing features in a series of aryl substituted ethyl-6-methyl-4-phenyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates. CrystEngComm. 2011;13(2):591–605. doi:10.1039/C0CE00045K
  • AliF, KhanKM, SalarU, et al. Dihydropyrimidones: as novel class of beta-glucuronidase inhibitors. Bioorg Med Chem. 2016;24(16):3624–3635. doi:10.1016/j.bmc.2016.06.00227325448
  • DondoniA, MassiA. Parallel synthesis of dihydropyrimidinones using Yb(III)-resin and polymer-supported scavengers under solvent-free conditions. A green chemistry approach to the Biginelli reaction. Tetrahedron Lett. 2001;42(45):7975–7978. doi:10.1016/S0040-4039(01)01728-2
  • MohamadpourF, LashkariM. Three-component reaction of β-keto esters, aromatic aldehydes and urea/thiourea promoted by caffeine, a green and natural, biodegradable catalyst for eco-safe Biginelli synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones derivatives under solvent-free conditions. J Serb Chem Soc. 2018;83(6):673–684.
  • LiuQ, PanN, XuJ, ZhangW, KongF. Microwave-assisted and iodine-catalyzed synthesis of dihydropyrimidin-2-thiones via biginelli reaction under solvent-free conditions. Synth Commun. 2013;43(1):139–146. doi:10.1080/00397911.2011.593289
  • MartinA, MorcilloN, LemusD, et al. Multicenter study of MTT and resazurin assays for testing susceptibility to first-line anti-tuberculosis drugs. Int J Tuberc Lung Dis. 2005;9(8):901–906.16104638
  • YoshikuniO, MayumiT, KenichiS. Inhibitory activity of quinolones against DNA gyrase of Mycobacterium tuberculosis. J Antimicrob Chemother. 2001;47:447–450. doi:10.1093/jac/47.4.44711266418
  • MiddlebrookG, ReggiardsZ, TigerttWD. Automable radiometric detection of growth of Mycobacterium tuberculosis in selective media. Am Rev Respir Dis. 1977;115:1067–1069.
  • ChandrashekharappaS, VenugopalaKN, TratratC, et al. Efficient synthesis and characterization of novel indolizines: exploration of in vitro COX-2 inhibitory activity and molecular modelling studies. New J Chem. 2018;42(7):4893–4901. doi:10.1039/C7NJ05010K
  • DainaA, MichielinO, ZoeteV. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2017;7:42717. doi:10.1038/srep4271728256516
  • VeberDF, JohnsonSR, ChengH-Y, SmithBR, WardKW, KoppleKD. Molecular properties that influence the oral bioavailability of drug candidates. J Med Chem. 2002;45(12):2615–2623. doi:10.1021/jm020017n12036371
  • LipinskiCA. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol. 2004;1(4):337–341. doi:10.1016/j.ddtec.2004.11.00724981612
  • YuDK. The contribution of P‐glycoprotein to pharmacokinetic drug‐drug interactions. J Clin Pharmacol. 1999;39(12):1203–1211. doi:10.1177/0091270992201200610586385
  • FrommM. Importance of P‐glycoprotein for drug disposition in humans. E J Clin Invest. 2003;33:6–9. doi:10.1046/j.1365-2362.33.s2.4.x
  • LinJH. CYP induction-mediated drug interactions: in vitro assessment and clinical implications. Pharm Res. 2006;23(6):1089–1116. doi:10.1007/s11095-006-0277-716718615