Exploring the impact of the innovative compound 3-(3-(4-hydroxy-2-oxo-2H-chromen-3-yl)-5-(pyridin-3-yl)-1H-pyrazol-1-yl) indolin-2-one on accelerating wound recovery

1. Byrd, A. L., Belkaid, Y. & Segre, J. A. The human skin Microbiome. Nat. Rev. Microbiol. 16, 143 (2018).

   Google Scholar 

2. Dandona, R. et al. Mortality due to road injuries in the States of india: The global burden of disease study 1990–2017. Lancet Public. Health. 5, e86 (2020).

   Google Scholar 

3. Graves, N., Phillips, C. J. & Harding, K. A narrative review of the epidemiology and economics of chronic wounds. Br. J. Dermatol. 187, 141 (2022).

   Google Scholar 

4. Rezvani Ghomi, E., Khalili, S., Nouri Khorasani, S., Esmaeely Neisiany, R. & Ramakrishna, S. Wound dressings: Current advances and future directions. J. Appl. Polym. Sci. 136, 47738 (2019).

   Google Scholar 

5. Bryson, A. L. & Doern, C. D. Wound cultures. In Clinical microbiology procedures handbook (eds. Leber, A. L. & Burnham, C. A.) 5th ed., Aerobic Bacteriology, Chap. 3.12 (John Wiley & Sons, Hoboken, NJ, (2023).

6. Ahovan, Z. A. et al. Antibacterial smart hydrogels: New hope for infectious wound management. Mater. Today Bio. 17, 100499 (2022).

   Google Scholar 

7. Batran, R. Z. et al. Synthesis and mechanistic insights of coumarinyl-Indolinone hybrids as potent inhibitors of leishmania major. Eur. J. Med. Chem. 288, 117392 (2025).

   Google Scholar 

8. Ebaid, M. S. et al. Identification of coumarin-chalcone and coumarin-pyrazoline derivatives as novel anti-toxoplasma gondii agents. Drug Des. Dev. Ther. 18, 5599 (2024).

   Google Scholar 

9. Batran, R. Z. et al. Design, synthesis and molecular modeling of pyrazoline based coumarin derivatives as tubulin polymerization inhibitors. J. Mol. Struct. 1318, 139123 (2024).

   Google Scholar 

10. Sabt, A. et al. New pyrazolylindolin-2-one based coumarin derivatives as anti-melanoma agents: Design, synthesis, dual BRAF V600E/VEGFR-2 inhibition, and computational studies. RSC Adv. 14, 5907 (2024).

    Google Scholar 

11. Batran, R. Z., Ahmed, E. Y., Nossier, E. S., Awad, H. M. & Latif, N. A. Anticancer activity of new triazolopyrimidine linked coumarin and quinolone hybrids: Synthesis, molecular modeling, TrkA, PI3K/AKT and EGFR Inhibition. J. Mol. Struct. 1305, 137790 (2024).

    Google Scholar 

12. Batran, R. Z., Sabt, A., Dziadek, J. & Kassem, A. F. Design, synthesis and computational studies of new azaheterocyclic coumarin derivatives as anti-mycobacterium tuberculosis agents targeting Enoyl acyl carrier protein reductase (InhA). RSC Adv. 14, 21763 (2024).

    Google Scholar 

13. Batran, R. Z., Ahmed, E. Y., Awad, H. M., Ali, K. A. & Latif, N. A. EGFR and PI3K/m-TOR inhibitors: Design, microwave assisted synthesis and anticancer activity of thiazole–coumarin hybrids. RSC Adv. 13, 29070 (2023).

    Google Scholar 

14. Sharifi-Rad, J. et al. Natural coumarins: Exploring the pharmacological complexity and underlying molecular mechanisms. Oxid. Med. Cell Longev. 6492346 (2021). (2021).

15. Giovannuzzi, S. et al. Coumarins effectively inhibit bacterial α-carbonic anhydrases. J. Enzyme Inhib. Med. Chem. 37, 333 (2022).

    Google Scholar 

16. Batran, R. Z. et al. 4-Phenylcoumarin derivatives as new HIV-1 nnrtis: Design, synthesis, biological activities, and computational studies. Bioorg. Chem. 141, 106918 (2023).

    Google Scholar 

17. Batran, R. Z., Khedr, M. A., Latif, N. A., El Aty, A. & Shehata, A. A. Synthesis, homology modeling, molecular docking, dynamics, and antifungal screening of new 4-hydroxycoumarin derivatives as potential chitinase inhibitors. J. Mol. Struct. 1180, 260 (2019).

    Google Scholar 

18. Bettia, N., Shiab, J. S., Kadhumc, A. A. & Al-Amieryd, A. A. Harnessing coumarin chemistry: Antibacterial, antifungal, and antioxidant profiling of novel coumarin derivatives. J. Med. Pharm. Chem. Res. 6, 1530 (2024).

    Google Scholar 

19. Afshar, M., Hassanzadeh-Taheri, M., Zardast, M. & Honarmand, M. Efficacy of topical application of coumarin on incisional wound healing in BALB/c mice. Iran. J. Dermatol. 23, 56 (2020).

    Google Scholar 

20. Sahoo, J. & Kumar, P. S. Biological evaluation and spectral characterization of 4-hydroxy coumarin analogues. J. Taibah Univ. Med. Sci. 10, 306 (2015).

    Google Scholar 

21. Dutra, F. V. et al. Coumarin/β-Cyclodextrin inclusion complexes promote acceleration and improvement of wound healing. ACS Appl. Mater. Interfaces. 16, 30900 (2024).

    Google Scholar 

22. Kim, T. Y. et al. Iridoid glycosides and coumarin glycoside derivatives from the roots of nymphoides peltata and their In vitro wound healing properties. Int. J. Mol. Sci. 25, 1268 (2024).

    Google Scholar 

23. De, S. et al. Pyridine: the scaffolds with significant clinical diversity. Rsc Adv. 12, 15385 (2022).

    Google Scholar 

24. Ali, I. et al. Synthesis and characterization of pyridine-based organic salts: Their antibacterial, antibiofilm and wound healing activities. Bioorg. Chem. 100, 103937 (2020).

    Google Scholar 

25. Batran, R. Z., Ahmed, E. Y., Awad, H. M. & Latif, N. A. Naturally based pyrazoline derivatives as aminopeptidase N, VEGFR2 and MMP9 inhibitors: Design, synthesis and molecular modeling. RSC Adv. 14, 22434 (2024).

    Google Scholar 

26. Sohn, E. H., Kim, S. N. & Lee, S. R. Melatonin’s impact on wound healing. Antioxidants 13, 1197 (2024).

    Google Scholar 

27. Elsayed, M. A., Elsayed, A. M. & Sroor, F. M. Novel biologically active pyridine derivatives: Synthesis, structure characterization, in vitro antimicrobial evaluation and structure-activity relationship. Med. Chem. Res. 33, 476 (2024).

    Google Scholar 

28. Li, G. et al. Pyrazole-containing pharmaceuticals: Target, pharmacological activity, and their SAR studies. RSC Med. Chem. 13, 1300 (2022).

    Google Scholar 

29. Seo, G. Y. et al. Novel naphthochalcone derivative accelerate dermal wound healing through induction of epithelial-mesenchymal transition of keratinocyte. J. Biomed. Sci. 22, 1 (2015).

    Google Scholar 

30. Shirinzadeh, H., Süzen, S., Altanlar, N. & Westwell, A. D. Antimicrobial activities of new Indole derivatives containing 1, 2, 4-triazole, 1, 3, 4-thiadiazole and carbothioamide. Turk. J. Pharm. Sci. 15, 291 (2018).

    Google Scholar 

31. Sabarees, G., Velmurugan, V., Gouthaman, S., Solomon, V. R. & Kandhasamy, S. Fabrication of quercetin-functionalized morpholine and pyridine Motifs-Laden silk fibroin nanofibers for effective wound healing in preclinical study. Pharmaceutics 16, 462 (2024).

    Google Scholar 

32. Elsayed, R. E., Madkour, T. M. & Azzam, R. A. Tailored-design of electrospun nanofiber cellulose acetate/poly (lactic acid) dressing Mats loaded with a newly synthesized sulfonamide analog exhibiting superior wound healing. Int. J. Biol. Macromol. 164, 1984 (2020).

    Google Scholar 

33. Qin, H. L., Zhang, Z. W., Ravindar, L. & Rakesh, K. P. Antibacterial activities with the structure-activity relationship of coumarin derivatives. Eur. J. Med. Chem. 207, 112832 (2020).

    Google Scholar 

34. Venugopala, K. N., Rashmi, V. & Odhav, B. Review on natural coumarin lead compounds for their Pharmacological activity. Biomed. Res. Int. 963248 2013 (2013).

35. Aatif, M. et al. Potential nitrogen-based heterocyclic compounds for treating infectious diseases: A literature review. Antibiotics 11, 1750 (2022).

    Google Scholar 

36. Sabt, A., Abdelrahman, M. T., Abdelraof, M. & Rashdan, H. R. Investigation of novel mucorales fungal inhibitors: Synthesis, in-silico study and anti-fungal potency of novel class of coumarin-6-sulfonamides-thiazole and thiadiazole hybrids. ChemistrySelect 7, e202200691 (2022).

    Google Scholar 

37. Abo-Salem, H. M. et al. Chitosan nanoparticles of new chromone-based sulfonamide derivatives as effective anti-microbial matrix for wound healing acceleration. Int. J. Biol. Macromol. 272, 132631 (2024).

    Google Scholar 

38. El-Sawy, E. R., Abdel-Aziz, M. S., Abdelmegeed, H. & Kirsch, G. Coumarins: Quorum sensing and biofilm formation Inhibition. Molecules 29, 4534 (2024).

    Google Scholar 

39. Sahoo, C. R. et al. Coumarin derivatives as promising antibacterial agent (s). Arab. J. Chem. 14, 102922 (2021).

    Google Scholar 

40. Cheke, R. S. et al. Molecular insights into coumarin analogues as antimicrobial agents: Recent developments in drug discovery. Antibiotics 11, 566 (2022).

    Google Scholar 

41. Kim, D. Y., Kang, Y. H. & Kang, M. K. Umbelliferone alleviates impaired wound healing and skin barrier dysfunction in high glucose-exposed dermal fibroblasts and diabetic skins. J. Mol. Med. 102, 1457 (2024).

    Google Scholar 

42. Adams, D. H., Shou, Q., Wohlmuth, H. & Cowin, A. J. Native Australian plant extracts differentially induce collagen I and collagen III in vitro and could be important targets for the development of new wound healing therapies. Fitoterapia 109, 45 (2016).

    Google Scholar 

43. Pooranachithra, M. et al. Unravelling the wound healing ability and mode of action of pyridine Carboxamide oxime using caenorhabditis elegans as potential prescreen wound model. Life Sci. 235, 116859 (2019).

    Google Scholar 

44. Morrison, D. K. MAP kinase pathways. Cold Spring Harb Perspect. Biol. 4, a011254 (2012).

    Google Scholar 

45. Abdelhafez, O. M. et al. Synthesis, anticoagulant and PIVKA-II induced by new 4-hydroxycoumarin derivatives. Bioorg. Med. Chem. 18, 3371 (2010).

    Google Scholar 

46. Nirusha, K. et al. Exploration of piperazine-citral sulfonyl derivatives: Antibacterial and in-silico studies against methicillin-resistant Staphylococcus aureus. Arch. Microbiol. 207, 562025 (2025).

    Google Scholar 

47. He, M. M. et al. Small-molecule Inhibition of TNF-α. Science 310, 1022 (2005).

    Google Scholar 

48. Gilbert, N. C. et al. Structural and mechanistic insights into 5-lipoxygenase Inhibition by natural products. Nat. Chem. Biol. 16, 783 (2020).

    Google Scholar 

49. Harman, C. A. et al. Structural basis of enantioselective Inhibition of cyclooxygenase-1 by S-alpha-substituted indomethacin ethanolamides. J. Biol. Chem. 282, 28096 (2007).

    Google Scholar 

50. Orlando, B. J. & Malkowski, M. G. Substrate-selective Inhibition of cyclooxygeanse-2 by Fenamic acid derivatives is dependent on peroxide tone. J. Biol. Chem. 291, 15069 (2016).

    Google Scholar 

51. Chaikuad, A. et al. A unique inhibitor binding site in ERK1/2 is associated with slow binding kinetics. Nat. Chem. Biol. 10, 853 (2014).

    Google Scholar 

52. MarvinSketch (version 22.2, by ChemAxon).

53. Morris, G. M. et al. AutoDock4 and AutoDockTools4: Automated Docking with selective receptor flexibility. J. Comput. Chem. 30, 2785 (2009).

    Google Scholar 

54. Trott, O. & Olson, A. J. AutoDock vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455 (2010).

    Google Scholar 

55. BIOVIA & Systèmes, D. Discovery Studio Visualizer, V25.1.0 (Dassault Systèmes, 2025).

56. Lee, J. et al. CHARMM-GUI input generator for NAMD, GROMACS, AMBER, OpenMM, and CHARMM/OpenMM simulations using the CHARMM36 additive force field. J. Chem. Theory Comput. 12, 405 (2016).

    Google Scholar 

57. Brooks, B. R. et al. Caflisch, A. CHARMM: The biomolecular simulation program. J. Comput. Chem. 30, 1545 (2009).

    Google Scholar 

58. Aboukhatwa, S. M. et al. Nicotinonitrile-derived apoptotic inducers: Design, synthesis, X-ray crystal structure and Pim kinase Inhibition. Bioorg. Chem. 129, 106126 (2022).

    Google Scholar 

59. Abraham, M. J. et al. High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX GROMACS, 1, 19 (2015).

    Google Scholar 

60. Kumari, R., Kumar, R., Open Source, Drug Discovery Consortium & Lynn, A. g_mmpbsa A GROMACS tool for high-throughput MM-PBSA calculations. J. Chem. Inf. Model. 54, 1951 (2014).

    Google Scholar 

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