In silico prediction of some indole derivatives against virb8 from Brucella suis and cyanobacterial membrane-bound manganese superoxide dismutase
DOI:
https://doi.org/10.56782/pps.412Keywords:
Indole, Virb8, Cyanobacterial, Antioxidant, Antimicrobial, CB DOCK-IIAbstract
This study investigates green chemistry methods to design the indole derivatives with potential medicinal properties. When benzaldehyde compounds react with phenyl hydrazine and ortho-phosphoric acid in an acidic environment, synthesized the indole derivatives. There are two proteins chosen from the protein data bank: the crystal structure of VirB8 from Brucella suis (PDB ID: 2BHM) for evaluation of antibacterial potential and a type of manganese superoxide dismutase (MnSOD) from cyanobacteria (PDB ID: 1GV3) for antioxidant potential. The molecule 3g had the best docking score of -10.4 with the crystal structure of VirB8 from Brucella suis (PDB ID 2BHM), which means it has a strong ability to bind to the target receptor. The molecule 3j had the best docking score of -10.4 against manganese superoxide dismutase (MnSOD) in the membrane of cyanobacteria (PDB ID: 1GV3), showing that it strongly attaches to the target receptor. The result suggests that it has a strong affinity for binding to the target receptor. This result indicates that it has a strong affinity for the target receptor. The metronidazole is taken as a standard for comparison purposes and has a molecular docking score of -6.5 against the crystal structure of VirB8 from Brucella suis. Ascorbic acid is used as a standard. It has a molecular docking score of -5.7 against manganese superoxide dismutase (MnSOD), which is attached to the membrane of cyanobacteria. The remaining design molecules demonstrated excellent docking scores for both proteins when compared to the standard molecules, metronidazole and ascorbic acid. In this study, ProtTox II Software was used to predict the in silico toxicity of all the design molecules. It was found that molecules 3l and metronidazole were respiratory toxic, while compounds 3g, 3k, 3p, and 3r were neurotoxic. All designed molecules were screened for the drug-likeness property and obeyed the criteria of the Lipinski rule of five.
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1. Terradot, L.; Bayliss, R.; Oomen, C.; Leonard, G. A.; Baron, C.; Waksman, G. Structures of two core subunits of the bacterial type IV secretion system, VirB8 from Brucella suis and ComB10 from Helicobacter pylori. Proc. Natl. Acad. Sci. 2005, 102 (12), 4596-4601. DOI: 10.1073/pnas.0408927102 DOI: https://doi.org/10.1073/pnas.0408927102
2. Atzenhofer, W.; Regelsberger, G.; Jacob, U.; Peschek, G. A.; Furtmüller, P. G.; Huber, R.; Obinger, C. The 2.0 Å resolution structure of the catalytic portion of a cyanobacterial membrane-bound manganese superoxide dismutase. J. Mol. Biol. 2002, 321 (3), 479-489. DOI: 10.1016/S0022-2836(02)00624-1 DOI: https://doi.org/10.1016/S0022-2836(02)00624-1
3. Paschos, A.; Patey, G.; Sivanesan, D.; Gao, C.; Bayliss, R.; Waksman, G.; O'callaghan, D.; Baron, C.; Dimerization and interactions of Brucella suis VirB8 with VirB4 and VirB10 are required for its biological activity. Proc. Natl. Acad. Sci. 2006, 103 (19), 7252-7257. DOI: 10.1073/pnas.0600862103 DOI: https://doi.org/10.1073/pnas.0600862103
4. Elkaeed, E.B.; Yousef, R.G.; Elkady, H.; Gobaara, I.M.; Alsfouk, A.A.; Husein, D.Z.; Ibrahim, I.M.; Metwaly, A.M.; Eissa, I.H. The assessment of anticancer and VEGFR-2 inhibitory activities of a new 1 H-indole derivative: in silico and in vitro approaches. Processes 2022, 10(7), Art. No: 1391. DOI: 10.3390/pr10071391 DOI: https://doi.org/10.3390/pr10071391
5. Regelsberger, G.; Atzenhofer, W.; Ruker, F.; Peschek, G.A.; Jakopitsch, C.; Paumann, M.; Furtmüller, P.G.; Obinger, C. Biochemical characterization of a membrane-bound manganese-containing superoxide dismutase from the cyanobacterium Anabaena PCC 7120. J. Biol. Chem. 2002, 277(46), 43615-43622. DOI: 10.1074/jbc.M207691200 DOI: https://doi.org/10.1074/jbc.M207691200
6. Surana, K.R.; Ahire, E.D.; Sonawane, V.N.; Talele, S.G.; Biomolecular and molecular docking: A modern tool in drug discovery and virtual screening of natural products. In Applied Pharmaceutical Practice and Nutraceuticals. Apple Academic Press 2021, 209-223. DOI: 10.1201/9781003054894 DOI: https://doi.org/10.1201/9781003054894-14
7. Hoppner, C.; Carle, A.; Sivanesan, D.; Hoeppner, S.; Baron, C. The putative lytic transglycosylase VirB1 from Brucellasuis interacts with the type IV secretion system core components VirB8, VirB9 and VirB11. Microbiology 2005, 151(11), 3469-3482. DOI: 10.1099/mic.0.28326-0 DOI: https://doi.org/10.1099/mic.0.28326-0
8. Priya, B.; Premanandh, J.; Dhanalakshmi, R.T.; Seethalakshmi, T.; Uma, L.; Prabaharan, D.; Subramanian, G.; Comparative analysis of cyanobacterial superoxide dismutases to discriminate canonical forms. BMC Genomics, 2007, 8, Art. No: 435. DOI: 10.1186/1471-2164-8-435 DOI: https://doi.org/10.1186/1471-2164-8-435
9. Andrieux, L.; Bourg, G.; Pirone, A.; O’Callaghan, D.; Patey, G. A single amino acid change in the transmembrane domain of the VirB8 protein affects dimerization, interaction with VirB10 and Brucella suis virulence. FEBS Lett. 2011, 585(15), 2431-2436. DOI: 10.1016/j.febslet.2011.07.004 DOI: https://doi.org/10.1016/j.febslet.2011.07.004
10. Shah, M.; Kumar, A.; Singh, A.K.; Singh, H.; Narasimhan, B.; Kumar, P.; In silico studies of Indole Derivatives as Antibacterial agents. J. Pharmacopuncture 2023, 26(2), 147-157. DOI: 10.3831/KPI.2023.26.2.147 DOI: https://doi.org/10.3831/KPI.2023.26.2.147
11. Parthiban, A.; Sivasankar, R.; Rajdev, B.; Asha, R.N.; Jeyakumar, T.C.; Periakaruppan, R.; Naidu, V.G.M. Synthesis, in vitro, in silico and DFT studies of indole curcumin derivatives as potential anticancer agents. J. Mol. Struc. 2022, 1270, Art. No: 133885. DOI: 10.1016/j.molstruc.2022.133885 DOI: https://doi.org/10.1016/j.molstruc.2022.133885
12. Kumari, A.; Singh, R.K. Synthesis, molecular docking and ADME prediction of 1H-indole/5-substituted indole derivatives as potential antioxidant and anti-inflammatory agents. Med. Chem. 2023, 19(2), 163-173. DOI: 10.2174/1573406418666220812152950 DOI: https://doi.org/10.2174/1573406418666220812152950
13. Dileep, K.V.; Remya, C.; Tintu, I.; Haridas, M.; Sadasivan, C. Interactions of selected indole derivatives with phospholipase A 2: in silico and in vitro analysis. J. Mol. Model. 2013, 19, 1811-1817. DOI: 10.1007/s00894-012-1741-4 DOI: https://doi.org/10.1007/s00894-012-1741-4
14. Balupuri, A.; Gadhe, C.G.; Balasubramanian, P.K.; Kothandan, G.; Cho, S.J. In silico study on indole derivatives as anti HIV-1 agents: a combined docking, molecular dynamics and 3D-QSAR study. Arch. Pharm. Res. 2014, 37, 1001-1015. DOI: 10.1007/s12272-013-0313-1 DOI: https://doi.org/10.1007/s12272-013-0313-1
15. Pingaew, R.; Mandi, P.; Prachayasittikul, V.; Thongnum, A.; Prachayasittikul, S.; Ruchirawat, S.; Prachayasittikul, V. Investigations on anticancer and antimalarial activities of indole-sulfonamide derivatives and in silico studies. ACS Omega 2021, 6(47), 31854-31868. DOI: 10.1021/acsomega.1c04552 DOI: https://doi.org/10.1021/acsomega.1c04552
16. Rudrapal, M.; Celik, I.; Chinnam, S.; Çevik, U.A.; Tallei, T.E.; Nizam, A.; Joy, F.; Abdellattif, M.H.; Walode, S.G. Analgesic and anti-inflammatory potential of indole derivatives. Polycyclic Aromatic Compounds 2023, 43(9), 7732-7753. DOI: 10.1080/10406638.2022.2139733 DOI: https://doi.org/10.1080/10406638.2022.2139733
17. Miller, A.F.; Superoxide dismutases: ancient enzymes and new insights. FEBS Lett. 2012, 586(5), 585-595. DOI: 10.1016/j.febslet.2011.10.048 DOI: https://doi.org/10.1016/j.febslet.2011.10.048
18. Uma, L.; Prabaharan, D.; Priya, B.; Subramanian, G.; Role of cyanobacterial oxidases in bioremediation-an overview. Al. Bio. Biotech. 2009, 251-261.
19. Venkataramanaa, C.H.S.; Sravania, K.R.; Singha, S.S.; Madhavanb, V.; In-silico ADME and toxcity studies of some novel indole derivatives. J. Appl. Pharm. Sci. 2011, 01(10), 159-162.
20. Surana, K.R.; Mahajan, S.K. In silico study of chromane ring compound rubranonoside from Plumeria rubra as anticancer potential. Trend. Sci. 2022, 19(24), 3305-3305. DOI: 10.48048/tis.2022.3305 DOI: https://doi.org/10.48048/tis.2022.3305
21. Surana, K.R.; Jadhav, P.S.; Shewale, H.S.; Wagh, D.B.; Mahajan, S.K.; Musale, J.V. In silico and Biological Evaluation of Anti-Inflammatory Activity of synthesized Benzimidazoles Derivatives. Biosci. Biotechnol. Res. Asia. 2024, 20(3), 1241-1253. DOI: 10.13005/bbra/3300 DOI: https://doi.org/10.13005/bbra/3300
22. Aher, S.N.; Sonawane, S.N.; Sonawane, P.R.; Surana, K.R.; Mahajan, S.K.; and Patil, D.M. In silico Drug Design, Synthesis and Evaluation of Anti-inflammatory Activity Pyrimidine Analogue. Biosci. Biotechnol. Res. Asia. 2024, 21(2), 741-753. DOI: 10.13005/bbra/3261 DOI: https://doi.org/10.13005/bbra/3261
23. Balekundri, A.; Ahire, E. D. Bacterial network construction and molecular docking approach to study interaction of Myristica fragrans on Acne infections: Molecular docking approach to study interaction of Myristica fragrans. Community Acquir. Infect. 2023,10. DOI: 10.54844/cai.2023.0326 DOI: https://doi.org/10.54844/cai.2023.0326
24. Ahire, E. D.; Kshirsagar, S. J. In Silico Investigation of Surfactants as Potential Permeation Glycoprotein Inhibitors for Formulation Development. Adv. Biores. 2023, 12, 115-120. DOI: 10.15515/abr.0976-4585.14.4.115120.
25. Smith, M.A.; Coinçon, M.; Paschos, A.; Jolicoeur, B.; Lavallée, P.; Sygusch, J.; Baron, C. Identification of the binding site of Brucella VirB8 interaction inhibitors. Chem. Biol. 2012, 19(8), 1041-1048. DOI: 10.1016/j.chembiol.2012.07.007 DOI: https://doi.org/10.1016/j.chembiol.2012.07.007
26. Priya, B.; Sivaprasanth, R.K.; Jensi, V.D.; Uma, L.; Subramanian, G.; Prabaharan, D. Characterization of manganese superoxide dismutase from a marine cyanobacterium Leptolyngbya valderiana BDU20041. Saline Syst. 2010, 6, Art. No: 6. DOI: 10.1186/1746-1448-6-6 DOI: https://doi.org/10.1186/1746-1448-6-6
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