1. bookVolume 72 (2022): Issue 1 (March 2022)
Journal Details
License
Format
Journal
First Published
28 Feb 2007
Publication timeframe
4 times per year
Languages
English
access type Open Access

Design, synthesis and molecular modeling study of substituted indoline-2-ones and spiro[indole-heterocycles] with potential activity against Gram-positive bacteria

Published Online: 30 Aug 2021
Page range: 79 - 95
Accepted: 17 Jan 2021
Journal Details
License
Format
Journal
First Published
28 Feb 2007
Publication timeframe
4 times per year
Languages
English
Abstract

Longstanding and firsthand infectious diseases are challenging community health threats. A new series of isatin derivatives bearing β-hydroxy ketone, chalcone, or spiro-heterocycle moiety, was synthesized in a good yield. Chemical structures of the synthesized compounds were elucidated using spectroscopic techniques and elemental analysis. Antibacterial activities of the compounds were then evaluated in vitro and by in silico modeling. The compounds were more active against Gram-positive bacteria, Staphylococcus aureus (MIC = 0.026–0.226 mmol L−1) and Bacillus subtilis (MIC = 0.348–1.723 mmol L–1) than against Gram-negative bacteria (MIC = 0.817–7.393 mmol L–1). Only 3-hydroxy-3-(2-(2,5-dimethylthiophen-3-yl)-2-oxoethyl)indolin-2-one (1b) was found as active as imipenem against S. aureus (MIC = 0.026 mmol L–1). In silico docking of the compounds in the binding sites of a homology modeled structure of S. aureus histidine kinase-Walk allowed us to shed light on the binding mode of these novel inhibitors. The highest antibacterial activity of 1b is consistent with its highest docking score values against S. aureus histidine kinase.

Keywords

1. S. K. Sridhar and A. Ramesh, Synthesis and pharmacological activities of hydrazones, Schiff and Mannich bases of isatin derivatives, Biol. Pharm. Bull. 24 (2001) 1149–1152; https://doi.org/10.1248/bpb.24.1149 Search in Google Scholar

2. M. Verma, S. N. Pandeya, K. N. Singh and J. P. Stables, Anticonvulsant activity of Schiff bases of isatin derivatives, Acta Pharm. 59 (2004) 49–56. Search in Google Scholar

3. A. K. Ádám, S. Grzegorz, J. B. Andrzej and M. K. György, Spiro[pyrrolidine-3,3′-oxindoles] and their indoline analogs as new 5-HT6 receptor chemotypes, Molecules 22 (2017) Article ID 2221; https://doi.org/10.3390/molecules22122221 Search in Google Scholar

4. E. Siddalingamurthy, K. M. Mahadevan, N. M. Jagadeesh and M. N. Kumara, Synthesis and docking study of 3-(N-alkyl/aryl piperidyl) indoles with serotonin-5HT, H1 and CCR2 antagonist receptors, Int. J. Pharm. Pharm. Sci. 6 (2014) 475–482. Search in Google Scholar

5. N. Karal, A. Gursoy, F. Kandemirli, N. Shvets, F. B. Kaynak, S. Ozbey, V. Kovalishyn and A. Dimoglo, Synthesis and structure-antituberculosis activity relationship of 1H-indole-2,3-dione derivatives, Bioorg. Med. Chem. 15 (2007) 5888–5904; https://doi.org/10.1016/j.bmc.2007.05.063 Search in Google Scholar

6. Q. Xu, L. Huang, J. Liu, L. Ma, T. Chen, J. Chen, F. Peng, D. Cao, Z. Yang, N. Qiu, J. Qiu, G. Wang, X. Liang, A. Peng, M. Xiang, Y. Wei and L. Chen, Design, synthesis and biological evaluation of thiazole- and indole-based derivatives for the treatment of type II diabetes, Eur. J. Med. Chem. 52 (2012) 70–81; https://doi.org/10.1016/j.ejmech.2012.03.006 Search in Google Scholar

7. A. I. Hashem, A. S. Youssef, K. A. Kandeel and W. S. Abou-Elmagd, Conversion of some 2(3H)-furanones bearing a pyrazolyl group into other heterocyclic systems with a study of their antiviral activity, Eur. J. Med. Chem. 42 (2007) 934–939; https://doi.org/10.1016/j.ejmech.2006.12.032 Search in Google Scholar

8. P. Kumar, S. Singh and M. R. F. Pratama, Synthesis of some novel 1H-indole derivatives with antibacterial activity and antifungal activity, Lett. App. NanoBioSci. 9 (2020) 961–967; https://doi.org/10.33263/LIANBS92.961967 Search in Google Scholar

9. R. V. Singh, N. Fahmi and M. K. Biyala, Coordination behavior and biopotency of N and S/O donor ligands with their palladium(II) and platinum(II) complexes, J. Iranian Chem. Soc. 40 (2005) 40–46; https://doi.org/https://doi.org/10.1007/BF03245778 Search in Google Scholar

10. K. Meenakshi, G. Sammaiah, M. Sarangapani and R. J. Venkateswar, Synthesis and antimicrobial activity of 1-N-piperidinomethyl isatin-3-[N-(quinolin-8-yloxy) acetyl] hydrazones, Indian J. Heterocycl. Chem. 16 (2006) 21–24. Search in Google Scholar

11. W. Hong, J. Li, Z. Chang, X. Tan, H. Yang, Y. Ouyang, Y. Yang, S. Kaur, I. C. Paterson, Y. F. Ngeow and H. Wang, Synthesis and biological evaluation of indole core-based derivatives with potent antibacterial activity against resistant bacterial pathogens, J. Antibiot. 70 (2017) 832–844; https://doi.org/10.1038/ja.2017.55 Search in Google Scholar

12. M. Taha, E A. J. Aldhamin, N. B. Almandil, El H. Anouar, N. Uddin, M. Alomari, F. Rahim, B. Adalat, M. Ibrahim, F. Nawaz, N. Iqbal, B. Alghanem, A. Altolayyan and K. M. Khan, Synthesis of indole based acetohydrazide analogs: Their in vitro and in silico thymidine phosphorylase studies, Bioorg. Chem. 98 (2020) Article ID 103745; https://doi.org/10.1016/j.bioorg.2020.103745 Search in Google Scholar

13. T. Tokunaga, H. W. Ewan, T. Umezome, K. Okazaki, Y. Ueki, K. Kumagai, S. Hourai, J. Nagamine, H. Seki, M. Taiji, H. Noguchi and R. Nagata, Oxindole derivatives as orally active potent growth hormone secretagogues, J. Med. Chem. 44 (2001) 4641–4649; https://doi.org/10.1021/jm0103763 Search in Google Scholar

14. T. Tokunaga, H. W. Ewan, J. Nagamine and R. Nagata, Structure-activity relationships of the oxindole growth hormone secretagogues, Bioorg. Med. Chem. Lett. 15 (2005) 1789–1792; https://doi.org/10.1016/j.bmcl.2005.02.042 Search in Google Scholar

15. P. E. Romo, B. Insuasty, R. Abonia, M. del Pilar Crespo and J. Quiroga, Synthesis of new oxindoles and determination of their antibacterial properties, Heteroatom Chem. 2020 (2020) Article ID 8021920 (9 pages); https://doi.org/10.1155/2020/8021920 Search in Google Scholar

16. K. N. Aneesrahman, K. Ramaiah, G. Rohini, G. P. Stefy, N. S. P. Bhuvanesh and A. Sreekanth, Synthesis and characterisations of copper(II) complexes of 5-methoxyisatin thiosemicarbazones: Effect of N-terminal substitution on DNA/protein binding and biological activities, Inorg. Chim. Acta 492 (2019) 131–141; https://doi.org/10.1016/j.ica.2019.04.019 Search in Google Scholar

17. A. A. El-Gendy and A. M. Ahmed, Synthesis and antimicrobial activity of some new 2-indolinone derived oximes and spiro-isoxazolines, Arch. Pharm. Res. 23 (2000) 310–314; https://doi.org/10.1007/bf02975439 Search in Google Scholar

18. A. L. Davis, D. R. Smith and T. J. McCord, Synthesis and microbiological properties of 3-amino-1-hydroxy-2-indolinone and related compounds, J. Med. Chem. 16 (1973) 1043–1045; https://doi.org/10.1021/jm00267a020 Search in Google Scholar

19. O. Sureyya and O. Z. Semiha, A Study of 3-substituted benzylidene-1,3-dihydro-indoline derivatives as antimicrobial and antiviral agents, Z. Naturforsch. C 64c (2009) 155–162; https://doi.org/10.1515/znc-2009-3-401 Search in Google Scholar

20. C. K. Ryu, J. Y. Lee, R. E. Park, M. Y. Ma and J. H. Nho, Synthesis and antifungal activity of 1H-indole-4,7-diones, Bioorg. Med. Chem. Lett. 17 (2007) 127–131; https://doi.org/10.1016/j.bmcl.2006.09.076 Search in Google Scholar

21. R. Hoessel, S. Leclerc, J. A. Endicott, M. E. Nobel, A. Lawrie, P. Tunnah, M. Leost, E. Damiens, D. Marie, D. Marko, E. Niederberger, W. Tang, G. Eisenbrand and L. Meijer, Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases, Nat. Cell Biol. 60 (1999) 60–67; https://doi.org/10.1038/9035 Search in Google Scholar

22. R. Han, Highlight on the studies of anticancer drugs derived from plants in China, Stem Cells 12 (1994) 53–63; https://doi.org/10.1002/stem.5530120110 Search in Google Scholar

23. H. P. Zhang, Y. Kamano, Y. Ichihara, H. Kizu, K. Komiyama, H. ltokawa and G. R. Pettit, Isolation and structure of convolutamydines B – D from marine bryozoan Amathia convolute, Tetrahedron 51 (1995) 5523–5528; https://doi.org/10.1016/0040-4020(95)00241-Y Search in Google Scholar

24. A. Abdel-Rahman, E. Keshk, M. Hanna and S. El-Bady, Synthesis and evaluation of some new spiro indoline-based heterocycles as potentially active antimicrobial agents, Bioorg. Med. Chem. 12 (2004) 2483–2488; https://doi.org/10.1016/j.bmc.2003.10.063 Search in Google Scholar

25. S. Rajeev, S. P. Siva, K. Leena, K. Shilpi and C. J. Subhash, Design and synthesis of spiro[indolethiazolidine]spiro[indole-pyrans] as antimicrobial agents, Bioorg. Med. Chem. Lett. 21 (2011) 5465–5469; https://doi.org/10.1016/j.bmcl.2011.06.121 Search in Google Scholar

26. P. Maryam, A. Sakineh, and M. Mojtaba, Synthesis and antibacterial evaluation of novel spiro[indole-pyrimidine]ones, J. Heterocycl. Chem. 55 (2018) 173–180; https://doi.org/10.1002/jhet.3021 Search in Google Scholar

27. T. Kitayama, R. Iwabuchi, S. Minagawa, S. Sawada, R. Okumura, K. Hoshino, J. Cappiello and R. Utsumi, Synthesis of a novel inhibitor against MRSA and VRE: preparation from zerumbone ring opening material showing histidine-kinase inhibition, Bioorg. Med. Chem. Lett. 17 (2007) 1098–1101; https://doi.org/10.1016/j.bmcl.2006.11.015 Search in Google Scholar

28. A. M. Stock, V. L. Robinson and P. N. Goudreau, Two-component signal transduction, Annu. Rev. Biochem. 69 (2000) 183–215; https://doi.org/10.1146/annurev.biochem.69.1.183 Search in Google Scholar

29. R. Gao, and A. M. Stock, Biological insights from structures of two-component proteins, Annu. Rev. Microbiol. 63 (2009) 133–154; https://doi.org/10.1146/annurev.micro.091208.073214 Search in Google Scholar

30. K. E. Wilke and E. E. Carlson, All signals lost, Sci. Transl. Med. 5 (2013) Article ID 203ps12; https://doi.org/10.1126/scitranslmed.3006670 Search in Google Scholar

31. A. E. Bem, N. Velikova, M. T. Pellicer, P. V. Baarlen, A. Marina and J. M. Wells, Bacterial histidine kinases as novel antibacterial drug targets, ACS Chem Biol. 10 (2015) 213–224; https://doi.org/10.1021/cb5007135 Search in Google Scholar

32. A. A. Radwan and W. Abdel-Mageed, In silico studies of quinoxaline-2-carboxamide 1,4-di-n-oxide derivatives as antimycobacterial agents, Molecules 19 (2014) 2247–2260; https://doi.org/10.3390/molecules19022247 Search in Google Scholar

33. A. A. Radwan, F. K. Alanazi and M. H. Al-Agami, 1,3,4-Thiadiazole and 1,2,4-triazole-3(4H)-thione bearing salicylate moiety: synthesis and evaluation as anti-Candida albicans, Braz. J. Pharm. Sci. 53 (2017) e15239; https://doi.org/10.1590/s2175-97902017000115239 Search in Google Scholar

34. T. Abul-Fadl, A. A. Radwan, H. A. Abdel-Aziz, B. Mohamed, I. A. Mohamad, K. Adnan, Novel Schiff bases of indoline-2,3-dione and nalidixic acid hydrazide: synthesis, in vitro antimycobacterial and in silico Mycobacterium tuberculosis (mtb) DNA gyrase inhibitory activity, Dig. J. Nanomater. Bios. 7 (2012) 329–336. Search in Google Scholar

35. T. Aboul-Fadl, A. A. Radwan, M. I. Attia, A. Al-Dhfyan and H. A. Abdel-Aziz, Schiff bases of indoline-2,3-dione (isatin) with potential antiproliferative activity, Chem. Cent. J. 6 (2012) Article ID 49; https://doi.org/10.1186/1752-153X-6-49 Search in Google Scholar

36. A. A. Radwan, Structure-based virtual screening for novel EGFR kinase inhibitors using the zinc database, Lat. Am. J. Pharm. 34 (2015) 1107–1112. Search in Google Scholar

37. A. A. Radwan, F. Al-Mohanna, F. K. Alanazi, P. S. Manogaran and A. Al-Dhfyan, Bioorg. Med. Chem. Lett. 26 (2016) 1664–1670; https://doi.org/10.1016/j.bmcl.2016.02.064 Search in Google Scholar

38. A. A. Radwan and F. K. Alanazi, In silico studies on novel inhibitors of MERS-CoV: Structure-based pharmacophore modeling, database screening and molecular docking, Trop. J. Pharm. Res. 17 (2018) 513–517; https://doi.org/http://dx.doi.org/10.4314/tjpr.v17i3.18 Search in Google Scholar

39. M. Kuroda, T. Ohta, I. Uchiyama, T. Baba, H. Yuzawa, I. Kobayashi, L. Cui, A. Oguchi, K. Aoki, Y. Nagai, J.-Q. Lian, T. Ito, M. Kanamori, H. Matsumaru, A. Maruyama, H. Murakami, A. Hosoyama, Y. Mizutani-Ui and K. Hiramatsu, Whole genome sequencing of methicillin resistant Staphylococcus aureus, Lancet 357 (2001) 1225–1240; https://doi.org/10.1016/S0140-6736(00)04403-2 Search in Google Scholar

40. C. Camacho, G. Coulouris, V. Avagyan, N. Ma, J. Papadopoulos, K. Bealer and T. L. Madden, BLAST+: architecture and applications, BMC Bioinform. 10 (2009) 421–430; https://doi.org/10.1186/1471-2105-10-421 Search in Google Scholar

41. F. András and A. Sali, Modeller: generation and refinement of homology-based protein structure models, Meth. Enzymol. 374 (2003) 461–491; https://doi.org/10.1016/S0076-6879(03)74020-8 Search in Google Scholar

42. P. T. Lang, S. R. Brozell, S. Mukherjee, E. F. Pettersen, E. C. Meng, V. Thomas, R. C. Rizzo, D. A. Case, T. L. James and I. D. Kuntz, DOCK 6: combining techniques to model RNA-small molecule complexes, RNA 15 (2009) 1219–1230; https://doi.org/10.1261/rna.1563609 Search in Google Scholar

43. Y. Cai, M. Su, A. Ahmad, X. Hu, J. Sang, L. Kong, X. Chen, C. Wang, J. Shuai and A. Han, Conformational dynamics of the essential sensor histidine kinase WalK, Acta Crystallogr. D 73 (2017) 793–803; https://doi.org/10.1107/S2059798317013043 Search in Google Scholar

44. E. Geisinger, E. A. George, J. Chen, T. W. Muir and R. P. Novick, Identification of ligand specificity determinants in AgrC, the Staphylococcus aureus quorum-sensing receptor, J. Biol. Chem. 283 (2008) 8930–8938; https://doi.org/10.1074/jbc.M710227200 Search in Google Scholar

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