Zinc Acetate as a Catalyst: Improved Method of Protection of Amino Group in Synthesis of Nucleobase Derivatives and its Biological Applications
Abstract
2-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-benzoisoquinoline-1,3(2H)-dione was synthesized by reacting 5-amino uracil with 1,8-naphthalic anhydride in the presence of zinc acetate as a catalyst and screened for the in-silico/in-vitro antimicrobial activities. All the analyzed physicochemical descriptors (viz. drug-likeness, bioactivity score, and absorption, distribution, metabolism, excretion, and toxicity (ADMET)) of the compound provide an impetus to the docking results obtained by simulating against the catalytic site of Escherichia coli peptide deformylase enzyme (PDF, PDB ID: 1G2A) and allosteric site of human immunodeficiency viruses (HIV) reverse transcriptase enzyme (PDB ID: 3MEC). Docking results revealed that the compound has interacted well with the amino acid residues Lys103, Lys101, and Pro 236 of non-invasive blood pressure (NIBP) of human immunodeficiency viruses (HIV) reverse transcriptase (RT) and Ile44, Gly89, Leu91, and Glu133 of peptide deformylase (PDF). The predicted free binding energy ΔG (-6.83 kcal/mol) showed that the compound formed a stable complex with PDF protein receptor, thus, can behave as a probable drug regimen in antibiotics. Whereas, the calculated total binding energy (-38.87 kcal/mol) alluded to the anti-HIV property of the compound as probable nucleoside reverse transcriptase inhibitor (NNRTI). In-vitro antibacterial screening, results exhibited promising inhibitory activity against Pseudomonas aeruginosa and E. coli (MIC value, 12.5 and 25 μg/mL, respectively).
Keywords:
Minimal inhibitory concentration, Docking, Peptide deformylase, Human immunodeficiency viruses reverse transcriptase, in-vitro, in-silico, Nucleoside reverse transcriptase inhibitorDOI
https://doi.org/10.25004/IJPSDR.2022.140605References
Anthony MP, Burrows JN, Duparc S, Moehrle JJ, Wells TNC. The global pipeline of new medicines for the control and elimination of malaria. Malaria Journal. 2012; 11:316. Available from: doi. org/10.1186/1475-2875-11-316
Yssel AEJ, Vanderleyden J, Steenackers HP. Repurposing of nucleoside and nucleobase derivative drugs as antibiotics and biofilm inhibitors. Journal of Antimicrobial Chemotherapy. 2017; 72(8): 2156-2170. Available from: doi.org/10.1093/jac/dkx151
Gaded V, Anand R. Nucleobase deaminases: a potential enzyme system for new therapies. RSC Advances. 2018; 8(42): 23567-23577. Available from: doi.org/10.1039/C8RA04112A
Yan J, Ji Y, Huang M, Li T, Liu Y, Lu S, Liu M. Nucleobase-inspired self-adhesive and inherently antibacterial hydrogel for wound dressing. ACS Materials Letters. 2020; 2(11):1375-1380. Available from: doi. org/10.1021/ acsmaterialslett.0c00304.
Pantazopoulou A, Diallinas G. Fungal nucleobase transporters. FEMS Microbiology Reviews. 2007; 31(6):657-675. Available from: 10.1111/j.1574- 6976.2007.00083.x
Łączkowski KZ, Biernasiuk A, Łączkowska AB, Misiura K, Malm A, Plech T, Paneth A. Synthesis, antibacterial activity, interaction with nucleobase and molecular docking studies of 4-formylbenzoic acid-based thiazoles. Medicinal Chemistry. 2016; 12(6):553-562. Available from: doi.org/10.2174/1573406412666160201121310.
Al-Azzawi AM, Hamd AS. Synthesis, Characterization, and Evaluation of Biological Activity of Novel Cyclic Imides Containing Heterocycles Based on 2, 5 disubstituted-1, 3, 4-thiadiazoles. Al-Anbar Journal of Veterinary Sciences. 2011; 4(2):152-164. ISSN:1999-6527
Filosa R, Peduto A, Di Micco S, de Caprariis P, Festa M, Petrella A, Capranico G, Bifulco G. Molecular modelling studies, synthesis and biological activity of a series of novel bisnaphthalimides and their development as new DNA topoisomerase II inhibitors. Bioorganic and Medicinal Chemistry. 2009; 17(1):13-24. Available from: doi. org/10.1016/j.bmc.2008.11.024.
Gallori E, Casalone E, Colella CM, Daly S, Polsinelli M. 1, 8-Naphthalic anhydride antidote enhances the toxic effects of captan and thiram fungicides on Azospirillum brasilense cells. Research in Microbiology. 1991; 142(9):1005-1012. Available from: doi. org/10.1016/0923-2508(91)90011-X.
Al-Azzawi AM, Sulaiman A. Synthesis, characterization and evaluat ion of the ant ibacterial act ivity of several new 1, 8-naphthalimides containing benzothiazole moiety. Kerbala Journal of Pharmaceutical Sciences. 2011; 111-123.
Marinov M, Kostova I, Naydenova E, Stoyanov N. Synthesis and antimicrobial activity of 1, 8-naphthalimide derivatives of nalidixic acid. Journal of Chemical Technology and Metallurgy. 2019; 54(6):1146-1156.
Tanaka FS, Wien RG, Hoffer BL. Synthesis of high specific activity 1, 8-naphthalic anhydride. Journal Labelled Compounds and Radiopharmaceuticals. 1984; 21(6):549-561. Available from: doi. org/10.1002/jlcr.2580210608
Inoue A, Jiang L, Lu F, Zhang Y. Genomic imprinting of Xist by maternal H3K27me3. Genes & Development. 2017; 31(19):1927- 1932. Available from: doi.org/10.1101/gad.304113.117
Łączkowski KZ, Biernasiuk A, Łączkowska AB, Zielińska S, Sałat K, Furgała A, Misiura K, Malm A. Synthesis, antimicrobial and anticonvulsant screening of a small library of tetrahydro-2 H-thiopyran-4-yl based thiazoles and selenazoles. Journal of Enzyme Inhibition and Medicinal Chemistry. 2016; 31(sup2): 24-39. Available from:10.1080/14756366.2016.1186020
Riccardi C, Capasso D, Coppola A, Platella C, Montesarchio D, Gaetano SD, Roviello GN, Musumeci D. Synthesis, antiproliferative activity, and DNA binding studies of nucleoamino acid-containing Pt(II) complexes. Pharmaceuticals. 2020; 13(10):284. Available from: 10.3390/ph13100284
Iigo M, Ando N, Hoshi A, Kuretani K. Effect of pyrimidines, purines and their nucleosides on antitumor activity of 5-fluorouracil against L-1210 leukemia. Journal of Pharmacobio-dynamics. 1982; 5(7):515-520. Available from: doi.org/10.1248/bpb1978.5.515
Barman K, Das G, Kalita JM, Dasgupta P. Design and molecular docking of sulfonamide derivatives. International Journal of Current Pharmaceutical Research. 2021; 13:93-97. Available from: doi. org/10.22159/ijcpr.2021v13i4.42752
Srivastava R, Gupta SK, Naaz F, Gupta PSS, Yadav M, Singh VK, Singh A, Rana MK, Gupta SK, Schols D, Singh RK. Alkylated benzimidazoles: Design, synthesis, docking, DFT analysis, ADMET property, molecular dynamics and activity against HIV and YFV. Computational Biology and Chemistry. 2020; 89:107400. Available from: doi.org/10.1016.2Fj.compbiolchem.2020.107400
Naaz F, Srivastava R, Singh A, Singh N, Verma R, Singh VK, Singh RK. Molecular modeling, synthesis, antibacterial and cytotoxicity evaluation of sulfonamide derivatives of benzimidazole, indazole, benzothiazole and thiazole. Bioorganic and Medicinal Chemistry. 2018; 26(12):3414-3428. Available from: doi.org/10.1016/j. bmc.2018.05.015
Yadav M, Srivastava R, Naaz F, Singh RK. Synthesis, docking, ADMET prediction, cytotoxicity and antimicrobial activity of oxathiadiazole derivatives. Computational Biology and Chemistry. 2018; 77:226- 239. Available from: doi.org/10.1016/j.compbiolchem.2018.10.008
Kuswandi A, Rusdin A, Tarawan VM, Goenawan H, Lesmana R, Muchtaridi M. Molecular docking study of the major compounds from Garcinia Atroviridis on human Sglt-2 protein transport using structure-based drug design method. International Journal of Applied Pharmaceutics. 2022; 14:138-143. Available from: doi. org/10.22159/ijap.2022v14i4.44390
Umar AB, Uzairu A, Shallangwa GA, Uba S. QSAR modelling and molecular docking studies for anti-cancer compounds against melanoma cell line SK-MEL-2. Heliyon. 2020;6(3):e03640. Available from: doi.org/10.1016/j.heliyon.2020.03640
Lazaridis T, Karplus M. Effective energy functions for protein structure prediction. Current Opinion in Structural Biology. 2000; 10(2):139-145. Available from: doi.org/10.1016/S0959- 440X(00)00063-4
Kitchen DB, Decornez H, Furr JR, Bajorath J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nature Reviews. Drug discovery. 2004; 3(11):935-949. Available from: doi.org/10.1038/nrd1549
Venkatachalam CM, Jiang X, Oldfield T, Waldman M. LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites. Journal of Molecular Graphics and Modelling. 2003;21(4):289-307. Available from: doi.org/10.1016/S1093- 3263(02)00164-x
Dogra D, Julka J, Kumar A. Insight into antimicrobic evaluation techniques and their role in better assessment of antimicrobic agents: A R eview. A sian J ournal o f P harmaceutical a nd C linical Research. 2021; 15:6-13. Available from: doi.org/10.22159/ajpcr. 2022.v15i1.43411
Goyal A. Spectral evaluation and antimicrobial activity of synthesized 4h-1,4-benzothiazines. Asian Journal of Pharmaceutical and Clinical Research. 2021; 14:66-69. Available from: doi. org/10.22159/ajpcr.2021.v14i6.41193
Prathipati P, Saxena AK. Evaluation of binary QSAR models derived from LUDI and MOE scoring functions for structure-based virtual screening. Journal of Chemical Information and Modeling. 2006; 46(1):39-51. Available from: doi.org/10.1021/ci050120w
Wang R, Lu Y, Wang S. Comparative evaluation of 11 scoring functions for molecular docking. Journal of Medicinal Chemistry. 2003; 46(12):2287-2303. Available from: doi.org/10.1021/ jm0203783
VK, Srivastava R, Gupta PSS, Naaz F, Chaurasia H, Mishra R, Rana MK, Singh RK. The anti-HIV potential of diarylpyrimidine derivatives as non-nucleoside reverse transcriptase inhibitors: Design, synthesis, docking, TOPKAT analysis and molecular dynamics simulations. Journal of Biomolecular Structure and Dynamics. 2020;1-18. Available from: doi.org/10.1080/07391102.2020.1748111
Dikshit A, Chaddha M, Singh RK, Misra K. Naphthaloyal group: A new selective amino protecting group for deoxynucleosides in oligonucleotide synthesis. Canadian Journal of Chemistry. 1988; 66: 2989-2994. Available from: doi.org/10.1139/v88-464
Singh VK, Chaurasia H, Mishra R, Srivastava R, Naaz F, Kumar P, Singh RK. Docking, ADMET predict ion, DFT analysis, synthesis, cytotoxicity, antibacterial screening and QSAR analysis of diarylpyrimidine derivatives. Journal of Molecular Structure. 2022; 1247:131400. Available from: doi.org/10.1016/j. molstruc.2021.131400
Mishra R, Chaurasia H, Singh VK, Naaz F, Singh RK. Molecular modeling, QSAR analysis and antimicrobial properties of Schiff base derivatives of isatin. Journal of Molecular Structure. 2021; 1243:130763. Avai lable f rom: doi .org/10.1016/j. molstruc.2021.130763
Chaurasia H, Singh VK, Mishra R, Yadav AK, Ram NK, Singh P, Singh RK. Molecular modeling, synthesis, and antimicrobial evaluation of benzimidazole nucleoside mimetics. Bioorganic Chemistry. 2021; 115:105227. Available from: doi.org/10.1016/j.bioorg.2021.10 5227
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