Synthesis of New 3-Arylaminophthalides and 3-Indolyl-phthalides using Ammonium Chloride, Evaluation of their Anti-Mycobacterial Potential and Docking Study

Avinash       Patil; Harleen       Duggal; Kamini    T.   Bagul; Sonali       Kamble; Pradeep       Lokhande; Rajesh       Gacche; Rohan       Meshram

doi:10.2174/1386207323666200422082754

Abstract

Objective: The study aims at the derivatization of “Phthalides” and synthesizes 3- arylaminophthalides & 3-indolyl-phthalides compounds, and evaluates their anti-tubercular and antioxidant activities. The study has also intended to employ the in silico methods for the identification of possible drug targets in Mycobacterium and evaluate the binding affinities of synthesized compounds.

Methods: This report briefly explains the synthesis of phthalide derivatives using ammonium chloride. The synthesized compounds were characterized using spectral analysis. Resazurin Microtiter Assay (REMA) plate method was used to demonstrate the anti-mycobacterial activity of the synthesized compounds. An in-silico pharmacophore probing approach was used for target identification in Mycobacterium. The structural level interaction between the identified putative drug target and synthesized phthalides was studied using Lamarckian genetic algorithm-based software.

Results and Discussion: In the present study, we report an effective, environmentally benign scheme for the synthesis of phthalide derivatives. Compounds 5c and 5d from the current series appear to possess good anti-mycobacterial activity. dCTP: deaminasedUTPase was identified as a putative drug target in Mycobacterium. The docking results clearly showed the interactive involvement of conserved residues of dCTP with the synthesized phthalide compounds.

Conclusion: On the eve of evolving anti-TB drug resistance, the data on anti-tubercular and allied activities of the compounds in the present study demonstrates the enormous significance of these newly synthesized derivatives as possible candidate leads in the development of novel anti-tubercular agents. The docking results from the current report provide a structural rationale for the promising anti-tubercular activity demonstrated by 3-arylaminophthalides and 3-indolyl-phthalides compounds.

Keywords: Deoxycytidine triphosphate (dCTP) deaminase, pharmacophore probing, ammonium chloride, 3-arylaminophthalides, 3-indolyl-phthalides, docking, MMGBSA, target identification.

« Previous Next »

[1] 
Sánchez, J.G.B.; Kouznetsov, V.V. Antimycobacterial susceptibility testing methods for natural products research. Braz. J. Microbiol.,  2010, 41(2), 270-277.
[http://dx.doi.org/10.1590/S1517-83822010000200001 ] [PMID:  24031490] 
[2] 
Hadifar, S.; Shamkhali, L.; Kargarpour Kamakoli, M.; Mostafaei, S.; Khanipour, S.; Mansoori, N.; Fateh, A.; Siadat, S.D.; Vaziri, F. Genetic diversity of Mycobacterium tuberculosis isolates causing pulmonary and extrapulmonary tuberculosis in the capital of Iran. Mol. Phylogenet. Evol.,  2019, 132, 46-52.
[http://dx.doi.org/10.1016/j.ympev.2018.11.019 ] [PMID:  30513341] 
[3] 
Banga, R.K.; Singh, J.; Dahuja, A.; Garg, R.S. Spinal tuberculosis - directly observed treatment and short course or daily anti tubercular therapy -are we over treating? Open Orthop. J.,  2018, 12, 380-388.
[http://dx.doi.org/10.2174/1874325001812010380 ] [PMID:  30369990] 
[4] 
Manginell, R.P.; Pimentel, A.S.; Mowry, C.D.; Mangan, M.A.; Moorman, M.W.; Allen, A.; Schares, E.S.; Achyuthan, K.E. Diagnostic potential of the pulsed discharged helium ionization detector (PDHID) for pathogenic Mycobacterial volatile biomarkers. J. Breath Res.,  2013, 7(3), 037107.
[http://dx.doi.org/10.1088/1752-7155/7/3/037107 ] [PMID:  23867723] 
[5] 
Azeez, A.; Ndege, J.; Mutambayi, R. Associated factors with unsuccessful tuberculosis treatment outcomes among tuberculosis/HIV coinfected patients with drug-resistant tuberculosis. Int. J. Mycobacteriol.,  2018, 7(4), 347-354.
[http://dx.doi.org/10.4103/ijmy.ijmy_140_18 ] [PMID:  30531033] 
[6] 
Sloan, K.B.; Koch, S.A. Effect of nucleophilicity and leaving group ability on the SN2 reactions of amines with (acyloxy) alkyl. alpha-halides: a product distribution study. J. Org. Chem.,  1983, 48(5), 635-640.
[http://dx.doi.org/10.1021/jo00153a002] 
[7] 
Heinisch, L.; Roemer, E.; Jütten, P.; Haas, W.; Werner, W.; Möllmann, U. Semisynthetic derivatives of madurahydroxylactone and their antibacterial activities. J. Antibiot. (Tokyo),  1999, 52(11), 1029-1041.
[http://dx.doi.org/10.7164/antibiotics.52.1029 ] [PMID:  10656576] 
[8] 
Ibironke, O.; Carranza, C.; Sarkar, S.; Torres, M.; Choi, H.T.; Nwoko, J.; Black, K.; Quintana-Belmares, R.; Osornio-Vargas, Á.; Ohman-Strickland, P.; Schwander, S. Urban Air Pollution Particulates Suppress Human T-Cell Responses to Mycobacterium Tuberculosis. Int. J. Environ. Res. Public Health,  2019, 16(21), E4112.
[http://dx.doi.org/10.3390/ijerph16214112 ] [PMID:  31731429] 
[9] 
Wei, Q.; Yang, J.; Li, L.; Su, Y.; Wang, A. Novel phthalide dimers from the aerial parts of Ligusticum sinense Oliv cv. Chaxiong. Fitoterapia,  2019, 137, 104174.
[http://dx.doi.org/10.1016/j.fitote.2019.104174 ] [PMID:  31100437] 
[10] 
Li, W.; Wu, Y.; Liu, X.; Yan, C.; Liu, D.; Pan, Y.; Yang, G.; Yin, F.; Weng, Z.; Zhao, D.; Chen, Z.; Cai, B. Antioxidant properties of cis-Z,Z′-3a.7a′,7a.3a′-dihydroxyligustilide on human umbilical vein endothelial cells in vitro. Molecules,  2013, 18(1), 520-534.
[http://dx.doi.org/10.3390/molecules18010520 ] [PMID:  23282538] 
[11] 
Juárez-Reyes, K.; Angeles-López, G.E.; Rivero-Cruz, I.; Bye, R.; Mata, R. Antinociceptive activity of Ligusticum porteri preparations and compounds. Pharm. Biol.,  2014, 52(1), 14-20.
[http://dx.doi.org/10.3109/13880209.2013.805235 ] [PMID:  24093628] 
[12] 
Xiao, B.; Yin, J.; Park, M.; Liu, J.; Li, J.L.; Kim, E.L.; Hong, J.; Chung, H.Y.; Jung, J.H. Design and synthesis of marine fungal phthalide derivatives as PPAR-γ agonists. Bioorg. Med. Chem.,  2012, 20(16), 4954-4961.
[http://dx.doi.org/10.1016/j.bmc.2012.06.039 ] [PMID:  22819190] 
[13] 
León, A.; Del-Ángel, M.; Ávila, J.L.; Delgado, G. Phthalides: distribution in nature, chemical reactivity, synthesis, and biological activity. Prog. Chem. Org. Nat. Prod.,  2017, 104, 127-246.
[http://dx.doi.org/10.1007/978-3-319-45618-8_2 ] [PMID:  28160212] 
[14] 
Li, D.Y.; Wei, Y.; Shi, M. Iron (III)-catalyzed 1, 3-functional group transposition reactions: synthetic protocol to access 3-substituted indoles. Asian J. Org. Chem.,  2016, 5(3), 423-427.
[http://dx.doi.org/10.1002/ajoc.201600037] 
[15] 
Mamidyala, S.K.; Cooper, M.A. Probing the reactivity of o-phthalaldehydic acid/methyl ester: synthesis of N-isoindolinones and 3-arylaminophthalides. Chem. Commun. (Camb.),  2013, 49(75), 8407-8409.
[http://dx.doi.org/10.1039/c3cc43838d ] [PMID:  23939425] 
[16] 
Lin, H.; Zang, Y.; Sun, X.; Lin, G. Highly efficient synthesis of unsymmetrical 3, 3′-bis (1H-indol-3-yl) methanes in water. Chin. J. Chem.,  2012, 30(10), 2309-2314.
[http://dx.doi.org/10.1002/cjoc.201200496] 
[17] 
Tang, H.; Zhang, X.; Song, A.; Zhang, Z.TsO.H. •H2O-catalyzed friedel-crafts of indoles of 3-hydroxyisobenzofuran-1 (3H)-one with indoles: highly synthesis of 3-indolyl-substituted phthalides. Modern Research in Catalysis,  2012, 1(02), 11.
[http://dx.doi.org/10.4236/mrc.2012.12002] 
[18] 
Lokhande, P.D.; Nawghare, B.R. New Synthesis of β-anilino-chalcones by regioselective oxidation of β-anilinodihydro-chalcones using iodine-DMSO. Synth. Commun.,  2014, 44, 3287-3295.
[http://dx.doi.org/10.1080/00397911.2012.667490] 
[19] 
Waghmare, S.R. Synthesis of biologically active derivative of quinoline alkaloids.. Ph.D Thesis, Savitribai Phule Pune University,
Pune , 2017.
[20] 
Chen, W.; Shi, L. Ammonium chloride-catalyzed carbon-sulfur bond formation in water. Catalysis. Commun.,  2008, 9, 1079-1081.
[21] 
Limaye, R.A.; Kumbhar, V.B.; Natu, A.D.; Paradkar, M.V.; Honmore, V.S.; Chauhan, R.R.; Gample, S.P.; Sarkar, D. One pot solvent free synthesis and in vitro antitubercular screening of 3-aracylphthalides against Mycobacterium tuberculosis. Bioorg. Med. Chem. Lett.,  2013, 23(3), 711-714.
[http://dx.doi.org/10.1016/j.bmcl.2012.11.097 ] [PMID:  23265877] 
[22] 
Ukhin, L.Y.; Suponitsky, K.Y.; Belousova, L.V.; Orlova, Z.I. A new synthesis of phthalimidines. Russ. Chem. Bull.,  2009, 58(12), 2478-2487.
[http://dx.doi.org/10.1007/s11172-009-0347-1] 
[23] 
Huang, G.; Liu, B.; Teng, M.; Chen, Y. Ammonium chloride–catalyzed one-pot synthesis of 4 (3 H)-quinazolinones under solvent-free conditions. Synth. Commun.,  2014, 44(12), 1786-1794.
[http://dx.doi.org/10.1080/00397911.2013.873467] 
[24] 
Liu, X.; Ouyang, S.; Yu, B.; Liu, Y.; Huang, K.; Gong, J.; Zheng, S.; Li, Z.; Li, H.; Jiang, H. PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res. ,  2010, 38(Web Server issue), W609-14.
[http://dx.doi.org/10.1093/nar/gkq300] [PMID: 20430828] 
[25] 
Björnberg, O.; Neuhard, J.; Nyman, P.O. A bifunctional dCTP deaminase-dUTP nucleotidohydrolase from the hyperthermophilic archaeon Methanocaldococcus jannaschii. J. Biol. Chem.,  2003, 278(23), 20667-20672.
[http://dx.doi.org/10.1074/jbc.M213010200 ] [PMID:  12670946] 
[26] 
Helt, S.S.; Thymark, M.; Harris, P.; Aagaard, C.; Dietrich, J.; Larsen, S.; Willemoes, M. Mechanism of dTTP inhibition of the bifunctional dCTP deaminase: dUTPase encoded by Mycobacterium tuberculosis. J. Mol. Biol.,  2008, 376(2), 554-569.
[http://dx.doi.org/10.1016/j.jmb.2007.11.099 ] [PMID:  18164314] 
[27] 
Chaturvedi, V.; Dwivedi, N.; Tripathi, R.P.; Sinha, S. Evaluation of Mycobacterium smegmatis as a possible surrogate screen for selecting molecules active against multi-drug resistant Mycobacterium tuberculosis. J. Gen. Appl. Microbiol.,  2007, 53(6), 333-337.
[http://dx.doi.org/10.2323/jgam.53.333 ] [PMID:  18187888] 
[28] 
Kamble, R.D.; Hese, S.V.; Meshram, R.J.; Kote, J.R.; Gacche, R.N.; Dawane, B.S. Green synthesis and in silico investigation of dihydro-2H-benzo [1, 3] oxazine derivatives as inhibitors of Mycobacterium tuberculosis. Med. Chem. Res.,  2015, 24(3), 1077-1088.
[http://dx.doi.org/10.1007/s00044-014-1165-z] 
[29] 
Khalifa, R.A.; Nasser, M.S.; Gomaa, A.A.; Osman, N.M.; Salem, H.M. Resazurin microtiter assay plate method for detection of susceptibility of multidrug resistant Mycobacterium tuberculosis to second-line anti-tuberculous drugs. Egypt. J. Chest Dis. Tuberc.,  2013, 62(2), 241-247.
[http://dx.doi.org/10.1016/j.ejcdt.2013.05.008] 
[30] 
Martin, A.; Camacho, M.; Portaels, F.; Palomino, J.C. Resazurin microtiter assay plate testing of Mycobacterium tuberculosis susceptibilities to second-line drugs: rapid, simple, and inexpensive method. Antimicrob. Agents Chemother.,  2003, 47(11), 3616-3619.
[http://dx.doi.org/10.1128/AAC.47.11.3616-3619.2003 ] [PMID:  14576129] 
[31] 
Taneja, N.K.; Tyagi, J.S. Resazurin reduction assays for screening of anti-tubercular compounds against dormant and actively growing Mycobacterium tuberculosis, Mycobacterium bovis BCG and Mycobacterium smegmatis. J. Antimicrob. Chemother.,  2007, 60(2), 288-293.
[http://dx.doi.org/10.1093/jac/dkm207 ] [PMID:  17586560] 
[32] 
Gacche, R.; Shaikh, R.; Pund, M.; Deshmukh, R. Cyclooxygenase inhibitory, cytotoxicity and free radical scavenging activities of selected medicinal plants used in indian traditional medicine. Pharmacogn. J.,  2011, 3(19), 57-64.
[http://dx.doi.org/10.5530/pj.2011.19.11] 
[33] 
Mohana, K.N.; Kumar, C.B.P. Synthesis and antioxidant activity of 2-amino-5-methylthiazol derivatives containing 1, 3, 4-oxadiazole-2-thiol moiety. ISRN Org. Chem.,  2013, 2013, 620718.
[34] 
Mladenović, M.; Mihailović, M.; Bogojević, D.; Matić, S.; Nićiforović, N.; Mihailović, V.; Vuković, N.; Sukdolak, S.; Solujić, S. In vitro antioxidant activity of selected 4-hydroxy-chromene-2-one derivatives-SAR, QSAR and DFT studies. Int. J. Mol. Sci.,  2011, 12(5), 2822-2841.
[http://dx.doi.org/10.3390/ijms12052822 ] [PMID:  21686153] 
[35] 
Sadasivam, S.; Manickman, A. Biochemical Methods for
Agricultural Sciences Publisher New Age International Pub. (P)
Limited.  1992.
[36] 
Ambhore, A.N.; Kamble, S.S.; Kadam, S.N.; Kamble, R.D.; Hebade, M.J.; Hese, S.V.; Gaikwad, M.V.; Meshram, R.J.; Gacche, R.N.; Dawane, B.S. Design, synthesis and in silico study of pyridine based 1,3,4-oxadiazole embedded hydrazinecarbothioamide derivatives as potent anti-tubercular agent. Comput. Biol. Chem.,  2019, 80, 54-65.
[http://dx.doi.org/10.1016/j.compbiolchem.2019.03.002 ] [PMID:  30901601] 
[37] 
Mogle, P.P.; Meshram, R.J.; Hese, S.V.; Kamble, R.D.; Kamble, S.S.; Gacche, R.N.; Dawane, B.S. Synthesis and molecular docking studies of a new series of bipyrazol-yl-thiazol-ylidenehydrazinecarbothioamide derivatives as potential antitubercular agents. MedChemComm,  2016, 7, 1405.
[http://dx.doi.org/10.1039/C6MD00085A] 
[38] 
Meshram, R.J.; Bagul, K.T.; Pawnikar, S.P.; Barage, S.H.; Kolte, B.S.; Gacche, R.N. Known compounds and new lessons: structural and electronic basis of flavonoid based bioactivities. J. Biomol. Struct. Dyn.,  2020, 38(4), 1168-1184.
[PMID:  30898030] 
[39] 
Shaikh, R.U.; Dawane, A.A.; Pawar, R.P.; Gond, D.S.; Meshram, R.J.; Gacche, R.N. Inhibition of Helicobacter pylori and Its Associate Urease by Labdane Diterpenoids Isolated from Andrographis paniculata. Phytother. Res.,  2016, 30(3), 412-417.
[http://dx.doi.org/10.1002/ptr.5542 ] [PMID:  26648323] 
[40] 
Patil, K.K.; Meshram, R.J.; Barage, S.H.; Gacche, R.N. Dietary
flavonoids inhibit the glycation of lens proteins: implications in the
management of diabetic cataract.  3 Biotech ,  2019, 9(2), 47.
[41] 
Huey, R.; Morris, G.M.; Olson, A.J.; Goodsell, D.S. A semiempirical free energy force field with charge-based desolvation. J. Comput. Chem.,  2007, 28(6), 1145-1152.
[http://dx.doi.org/10.1002/jcc.20634 ] [PMID:  17274016] 
[42] 
Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.E.; Belew, R.K.; Olson, A.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem.,  1998, 19(14), 1639-1662.
[http://dx.doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B] 
[43] 
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] 
[44] 
Miteva, M.A.; Guyon, F. Tufféry, P. Frog2: Efficient 3D conformation ensemble generator for small compounds. Nucleic Acids Res.,  2010, 38, 622-627.
[http://dx.doi.org/10.1093/nar/gkq325] 
[45] 
Rappe, A.K.; Colwell, K.S.; Casewit, C.J. Application of a universal force field to metal complexes. Inorg. Chem.,  1993, 32(16), 3438-3450.
[http://dx.doi.org/10.1021/ic00068a012] 
[46] 
Rappé, A.K.; Casewit, C.J.; Colwell, K.S.; Goddard, W.A., III; Skiff, W.M. UFF, a full periodic table force field for molecular mechanics and molecular dynamics simulations. J. Am. Chem. Soc.,  1992, 114(25), 10024-10035.
[http://dx.doi.org/10.1021/ja00051a040] 
[47] 
Kamble, R.D.; Meshram, R.J.; Hese, S.V.; More, R.A.; Kamble, S.S.; Gacche, R.N.; Dawane, B.S. Synthesis and in silico investigation of thiazoles bearing pyrazoles derivatives as anti inflammatory agents. Comput. Biol. Chem.,  2016, 61, 86-96.
[http://dx.doi.org/10.1016/j.compbiolchem.2016.01.007 ] [PMID:  26844536] 
[48] 
Spyrakis, F.; Amadasi, A.; Fornabaio, M.; Abraham, D.J.; Mozzarelli, A.; Kellogg, G.E.; Cozzini, P. The consequences of scoring docked ligand conformations using free energy correlations. Eur. J. Med. Chem.,  2007, 42(7), 921-933.
[http://dx.doi.org/10.1016/j.ejmech.2006.12.037 ] [PMID:  17346861] 
[49] 
Genheden, S.; Ryde, U. The MM/PBSA and MM/GBSA methods to estimate ligand-binding affinities. Expert Opin. Drug Discov.,  2015, 10(5), 449-461.
[http://dx.doi.org/10.1517/17460441.2015.1032936 ] [PMID:  25835573] 
[50] 
Du, J.; Sun, H.; Xi, L.; Li, J.; Yang, Y.; Liu, H.; Yao, X. Molecular modeling study of checkpoint kinase 1 inhibitors by multiple docking strategies and prime/MM-GBSA calculation. J. Comput. Chem.,  2011, 32(13), 2800-2809.
[http://dx.doi.org/10.1002/jcc.21859 ] [PMID:  21717478] 
[51] 
Palrecha, S.; Lakade, D.; Kulkarni, A.; Pal, J.K.; Joshi, M. Computational insights into the interaction of small molecule inhibitors with HRI kinase domain. J. Biomol. Struct. Dyn.,  2019, 37(7), 1715-1723.
[http://dx.doi.org/10.1080/07391102.2018.1465850 ] [PMID:  29663856] 
[52] 
Case, D.A.; Cheatham, T.E., III; Darden, T.; Gohlke, H.; Luo, R.; Merz, K.M., Jr; Onufriev, A.; Simmerling, C.; Wang, B.; Woods, R.J. The Amber biomolecular simulation programs. J. Comput. Chem.,  2005, 26(16), 1668-1688.
[http://dx.doi.org/10.1002/jcc.20290 ] [PMID:  16200636] 
[53] 
Ylilauri, M.; Pentikäinen, O.T. MMGBSA as a tool to understand the binding affinities of filamin-peptide interactions. J. Chem. Inf. Model.,  2013, 53(10), 2626-2633.
[http://dx.doi.org/10.1021/ci4002475 ] [PMID:  23988151] 
[54] 
Connolly, M.L. Analytical molecular surface calculation. J. Appl. Cryst.,  1983, 16(5), 548-558.
[http://dx.doi.org/10.1107/S0021889883010985] 
[55] 
Jorgensen, W.L.; Tirado-Rives, J. The OPLS [optimized potentials for liquid simulations] potential functions for proteins, energy minimizations for crystals of cyclic peptides and crambin. J. Am. Chem. Soc.,  1988, 110(6), 1657-1666.
[http://dx.doi.org/10.1021/ja00214a001 ] [PMID:  27557051] 
[56] 
Khattab, S.N.; Hassan, S.Y.; El-Faham, A.; El Massry, A.M.M.; Amer, A. Reaction of phthalaldehydic acid with different substituted aniline as well as hydrazine derivatives. J. Heterocycl. Chem.,  2007, 44(3), 617-626.
[http://dx.doi.org/10.1002/jhet.5570440317] 
[57] 
Sloan, K.B.; Koch, S.A. Further reactions of 3-hydroxy-1 (3H)-isobenzofuranone with amines. J. Heterocycl. Chem.,  1985, 22(2), 429-432.
[http://dx.doi.org/10.1002/jhet.5570220242] 
[58] 
Kessar, S.V.; Singh Mankotia, A.K.; Agnihotri, K.R. Intramolecular Photoreactions of 2-Formylbenzamides and 2-Formylbenzylarnines. J. Chem. Soc. Chem. Commun.,  1993, 598.
[http://dx.doi.org/10.1039/c39930000598] 
[59] 
Chen, F.; Lei, M.; Hu, L. Synthesis of 2-substituted-3-(1 H-indol-3-yl) isoindolin-1-one derivatives in water under catalyst-free conditions. Green Chem.,  2014, 16(5), 2472-2479.
[http://dx.doi.org/10.1039/c3gc41882k] 
[60] 
Beck, J.J.; Chou, S.C. The structural diversity of phthalides from the Apiaceae. J. Nat. Prod.,  2007, 70(5), 891-900.
[http://dx.doi.org/10.1021/np0605586 ] [PMID:  17477571] 
[61] 
Marvadi, S.K.; Krishna, V.S.; Sriram, D.; Kantevari, S. Synthesis of novel morpholine, thiomorpholine and N-substituted piperazine coupled 2-(thiophen-2-yl)dihydroquinolines as potent inhibitors of Mycobacterium tuberculosis. Eur. J. Med. Chem.,  2019, 164, 171-178.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.043 ] [PMID:  30594675] 
[62] 
Thompson, A.M.; Blaser, A.; Palmer, B.D.; Anderson, R.F.; Shinde, S.S.; Launay, D.; Chatelain, E.; Maes, L.; Franzblau, S.G.; Wan, B.; Wang, Y.; Ma, Z.; Denny, W.A. 6-Nitro-2,3-dihydroimidazo[2,1-b][1,3]thiazoles: Facile synthesis and comparative appraisal against tuberculosis and neglected tropical diseases. Bioorg. Med. Chem. Lett.,  2017, 27(11), 2583-2589.
[http://dx.doi.org/10.1016/j.bmcl.2017.03.069 ] [PMID:  28462832] 
[63] 
Kumar, A.; Farhana, A.; Guidry, L.; Saini, V.; Hondalus, M.; Steyn, A.J. Redox homeostasis in mycobacteria: the key to tuberculosis control?  Expert Rev. Mol. Med. ,  2011, 13e39 
[http://dx.doi.org/10.1017/S1462399411002079] [PMID: 22172201] 
[64] 
Venugopala, K.N.; Chandrashekharappa, S.; Pillay, M.; Abdallah, H.H.; Mahomoodally, F.M.; Bhandary, S.; Chopra, D.; Attimarad, M.; Aldhubiab, B.E.; Nair, A.B.; Sreeharsha, N.; Morsy, M.A.; Pottathil, S.; Venugopala, R.; Odhav, B.; Mlisana, K. Computational, crystallographic studies, cytotoxicity and anti-tubercular activity of substituted 7-methoxy-indolizine analogues. PLoS One,  2019, 14(6), e0217270.
[http://dx.doi.org/10.1371/journal.pone.0217270 ] [PMID:  31163040] 
[65] 
Lv, K.; Li, L.; Wang, B.; Liu, M.; Wang, B.; Shen, W.; Guo, H.; Lu, Y. Design, synthesis and antimycobacterial activity of novel imidazo[1,2-a]pyridine-3-carboxamide derivatives. Eur. J. Med. Chem.,  2017, 137, 117-125.
[http://dx.doi.org/10.1016/j.ejmech.2017.05.044 ] [PMID:  28577507] 
[66] 
Wang, X.; Shen, Y.; Wang, S.; Li, S.; Zhang, W.; Liu, X.; Lai, L.; Pei, J. Li. H. PharmMapper 2017 update: a web server for potential drug target identification with a comprehensive target pharmacophore database. Nucleic Acids Res.,  2017, 45, 356-360.
[http://dx.doi.org/10.1093/nar/gkx374] 
[67] 
Pecsi, I.; Hirmondo, R.; Brown, A.C.; Lopata, A.; Parish, T.; Vertessy, B.G.; Tóth, J. The dUTPase enzyme is essential in Mycobacterium smegmatis. PLoS One,  2012, 7(5), e37461.
[http://dx.doi.org/10.1371/journal.pone.0037461 ] [PMID:  22655049] 
[68] 
Johansson, E.; Fanø, M.; Bynck, J.H.; Neuhard, J.; Larsen, S.; Sigurskjold, B.W.; Christensen, U.; Willemoës, M. Structures of dCTP deaminase from Escherichia coli with bound substrate and product: reaction mechanism and determinants of mono- and bifunctionality for a family of enzymes. J. Biol. Chem.,  2005, 280(4), 3051-3059.
[http://dx.doi.org/10.1074/jbc.M409534200 ] [PMID:  15539408] 
[69] 
Oehlenschlæger, C.B.; Løvgreen, M.N.; Reinauer, E.; Lehtinen, E.; Pind, M.L.L.; Harris, P.; Martinussen, J.; Willemoës, M. Bacillus halodurans strain C125 encodes and synthesizes enzymes from both known pathways to form dUMP directly from cytosine deoxyribonucleotides. Appl. Environ. Microbiol.,  2015, 81(10), 3395-3404.
[http://dx.doi.org/10.1128/AEM.00268-15 ] [PMID:  25746996] 
[70] 
Thymark, M.; Johansson, E.; Larsen, S.; Willemoës, M. Mutational analysis of the nucleotide binding site of Escherichia coli dCTP deaminase. Arch. Biochem. Biophys.,  2008, 470(1), 20-26.
[http://dx.doi.org/10.1016/j.abb.2007.10.013 ] [PMID:  17996716] 
[71] 
Huffman, J.L.; Li, H.; White, R.H.; Tainer, J.A. Structural basis for recognition and catalysis by the bifunctional dCTP deaminase and dUTPase from Methanococcus jannaschii. J. Mol. Biol.,  2003, 331(4), 885-896.
[http://dx.doi.org/10.1016/S0022-2836(03)00789-7 ] [PMID:  12909016] 
[72] 
Johansson, E.; Björnberg, O.; Nyman, P.O.; Larsen, S. Structure of the bifunctional dCTP deaminase-dUTPase from Methanocaldococcus jannaschii and its relation to other homotrimeric dUTPases. J. Biol. Chem.,  2003, 278(30), 27916-27922.
[http://dx.doi.org/10.1074/jbc.M304361200 ] [PMID:  12756253] 
[73] 
Zhang, J.; Peng, X.; Wei, G.; Su, D. NBPA: a cerebral ischaemic protective agent. Clin. Exp. Pharmacol. Physiol.,  1999, 26(10), 845-846.
[http://dx.doi.org/10.1046/j.1440-1681.1999.03144.x ] [PMID:  10549420] 

Rights & Permissions Print Cite

Article Metrics

14

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1386207323666200422082754	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402

Combinatorial Chemistry & High Throughput Screening

Synthesis of New 3-Arylaminophthalides and 3-Indolyl-phthalides using Ammonium Chloride, Evaluation of their Anti-Mycobacterial Potential and Docking Study

Abstract Play Pause

Related Journals

Abstract