Design, Synthesis, and Activity Assessment of Fudosteine Derivatives for Chronic Respiratory Disorders

doi:10.6023/cjoc202409029

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (7): 2566-2576.DOI: 10.6023/cjoc202409029 Previous Articles Next Articles

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慢性呼吸系统疾病药物福多司坦衍生物的设计、合成及活性评价

孙茂茹^a, 桂腾摇^a, 陈聪地^b, 杨鸿均^a^,^*(), 李雪锋^a

^a 西南民族大学化学与环境学院国家民委基础化学重点实验室成都 610041
^b 成都师范学院化学与生命科学学院成都 611130

收稿日期:2024-11-05 修回日期:2024-12-03 发布日期:2025-01-10
通讯作者: 杨鸿均
基金资助:
四川省功能分子结构优化与应用重点实验室（成都师范学院）(2023GNFZ-05); 西南民族大学中央高校优秀学生培养(320022350036)

Design, Synthesis, and Activity Assessment of Fudosteine Derivatives for Chronic Respiratory Disorders

Maoru Sun^a, Tengyao Gui^a, Congdi Chen^b, Hongjun Yang^a^,^*(), Xuefeng Li^a

^a Key Laboratory of General Chemistry of the National Ethnic Affairs Commission, School of Chemistry and Environment, Southwest Minzu University, Chengdu 610041
^b College of Chemistry and Life Science, Chengdu Normal University, Chengdu 611130

Received:2024-11-05 Revised:2024-12-03 Published:2025-01-10
Contact: Hongjun Yang
Supported by:
Sichuan Provincial Key Laboratory for Structural Optimization and Application of Functional Molecules, Chengdu Normal University(2023GNFZ-05); Southwest University for Nationalities Central University Excellent Student Training Project(320022350036)

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Abstract

Chronic obstructive pulmonary disease (COPD) has garnered increased attention as a result of its persistent symptoms, which undermine patientsʼ quality of life. Fudosteine has substantial advantages in the treatment of COPD due to its high efficacy and low adverse effects. In this study, Fudosteine sulfonamide derivatives Series I and amine derivatives Series II were designed and synthesized, and their biological activities were evaluated. The results showed that compound 6f had outstanding anti-inflammatory action with an IC₅₀ of 1.08 mmol/L, and a higher antioxidant capacity than the lead molecule. At the same time, molecular docking investigations have revealed that compound 6f establishes hydrogen bonds and hydrophobic contacts with the MUC5AC protein. Furthermore, derivative 1f inhibited PDE4A1 enzyme activity five times more than Fudosteine. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging tests demonstrated that all examined substances had higher antioxidant activity than Fudosteine. This study established a solid foundation for further research into COPD drug therapy.

Key words: Fudosteine, chronic obstructive pulmonary disease (COPD), amine derivatives, MUC5AC

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Maoru Sun, Tengyao Gui, Congdi Chen, Hongjun Yang, Xuefeng Li. Design, Synthesis, and Activity Assessment of Fudosteine Derivatives for Chronic Respiratory Disorders[J]. Chinese Journal of Organic Chemistry, 2025, 45(7): 2566-2576.

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References 29

[1]	Sahu S. K.; Rain M. D. M.; Vyas M. Eur. J. Med. Chem. Rep. 2024, 11, 100159.
[2]	Fricke-Galindo I.; Garcia-Carmona S.; Alanis-Ponce J.; Perez- Rubio G.; Ramirez-Venegas A.; Montiel-Lopez F.; Robles Her- nandez R.; Hernandez-Zenteno R. J.; Valencia-Perez Rea D.; Bautista-Becerril B.; Ramirez-Diaz M. E.; Cruz-Vicente F.; Martinez-Gomez M. L.; Sansores R.; Falfan-Valencia R. Heliyon 2024, 10, e28675.
[3]	Zeng X.; Lan Y.; Xiao J.; Hu L.; Tan L.; Liang M.; Wang X.; Lu S.; Peng T.; Long F. Expert Rev. Proteomic. 2023, 19, 311.
[4]	Yadav A. K.; Gu W.; Zhang T.; Xu X.; Yu L. COPD: J. Chronic Obstruct. Pulm. Dis. 2023, 20, 197.
[5]	Doña E.; Reinoso-Arija R.; Carrasco-Hernandez L.; Doménech A.; Dorado A.; Lopez-Campos J. L. J. Clin. Med. 2023, 12, 5293.
[6]	Durham A. L.; Adcock I. M. Lung Cancer 2015, 90, 121. doi: 10.1016/j.lungcan.2015.08.017 pmid: 26363803
[7]	Prediletto I.; Giancotti G.; Nava S. J. Clin. Med. 2023, 12, 3369.
[8]	Osoata G. O.; Hanazawa T.; Brindicci C.; Ito M.; Barnes P. J.; Kharitonov S.; Ito K. Chest 2009, 135, 1513. doi: S0012-3692(09)60355-X pmid: 19188555
[9]	Antonela Antoniu S. Expert Opin. Invest. Drug 2008, 18, 105.
[10]	Ferraro M.; Di Vincenzo S.; Sangiorgi C.; Leto Barone S.; Gangemi S.; Lanata L.; Pace E. Pharmaceuticals 2022, 15, 218.
[11]	Ueno-Iio T.; Shibakura M.; Iio K.; Tanimoto Y.; Kanehiro A.; Tanimoto M.; Kataoka M. Life Sci. 2013, 92, 1015. doi: 10.1016/j.lfs.2013.03.022 pmid: 23583570
[12]	Adeloye D.; Song P.; Zhu Y.; Campbell H.; Sheikh A.; Rudan I. Lancet Respir. Med. 2022, 10, 447. doi: 10.1016/S2213-2600(21)00511-7 pmid: 35279265
[13]	Han H.; Peng G.; Meister M.; Yao H.; Yang J. J.; Zou M.-H.; Liu Z.-R.; Ji X. Front. Pharmacol. 2021, 12, 726586.
[14]	Barnes P. J. Redox Biol. 2020, 33, 101544.
[15]	Barnes P. J. Clin. Sci. 2017, 131, 1541.
[16]	Negro R. W. D. Lung 2008, 186, 70.
[17]	Cazzola M.; Page C. P.; Wedzicha J. A.; Celli B. R.; Anzueto A.; Matera M. G. Respir. Res. 2023, 24, 194.
[18]	Barsh G. S.; Van Buren E.; Radicioni G.; Lester S.; O’Neal W. K.; Dang H.; Kasela S.; Garudadri S.; Curtis J. L.; Han M. K.; Krishnan J. A.; Wan E. S.; Silverman E. K.; Hastie A.; Ortega V. E.; Lappalainen T.; Nawijn M. C.; Berge M. v. d.; Christenson S. A.; Li Y.; Cho M. H.; Kesimer M.; Kelada S. N. P. Plos Genetics 2023, 19, e1010445.
[19]	Fu H.-T.; Zhang Y.; Zhang P.; Wu H.; Sun X.-Q.; Shen S.-Y.; Dou D.-B. Transl. Cancer Res. 2021, 10, 4047.
[20]	Radicioni G.; Ceppe A.; Ford A. A.; Alexis N. E.; Barr R. G.; Bleecker E. R.; Christenson S. A.; Cooper C. B.; Han M. K.; Hansel N. N.; Hastie A. T.; Hoffman E. A.; Kanner R. E.; Martinez F. J.; Ozkan E.; Paine R.; Woodruff P. G.; O'Neal W. K.; Boucher R. C.; Kesimer M. Lancet Respir. Med. 2021, 9, 1241. doi: 10.1016/S2213-2600(21)00079-5 pmid: 34058148
[21]	Komatsu H.; Yamaguchi S.; Komorita N.; Goto K.; Takagi S.; Ochi H.; Okumoto T. Pulm. Pharmacol. Ther. 2005, 18, 121.
[22]	Carpenter J.; Wang Y.; Gupta R.; Li Y.; Haridass P.; Subramani D. B.; Reidel B.; Morton L.; Ridley C.; O'Neal W. K.; Buisine M.-P.; Ehre C.; Thornton D. J.; Kesimer M. Proc. Natl. Acad. Sci 2021, 118, e2104490118.
[23]	Nunes J. H. B.; Nakahata D. H.; Corbi P. P.; Paiva R. E. F. D. Coord. Chem. Rev. 2023, 490, 215228.
[24]	Mahapatra M.; Mekap S. K.; Mal S.; Sahoo J.; Sahoo S. K.; Paidesetty S. K. Arch. Pharm. 2023, 356, 2200508.
[25]	Ghomashi R.; Ghomashi S.; Aghaei H.; Massah A. R. Curr. Med. Chem. 2023, 30, 407.
[26]	Whittaker H.; Rothnie K. J.; Quint J. K. Thorax 2024, 79, 202.
[27]	Rubio M. L.; Martin-Mosquero M. C.; Ortega M.; Peces-Barba G. Chest 2004, 125, 1500.
[28]	Wang Y.; Wang H.; Yang G.; Hao Q.; Yang K.; Shen H.; Wang Y.; Wang J. Eur. J. Med. Chem. 2023, 256, 115374.
[29]	Li G.; He D.; Cai X.; Guan W.; Zhang Y.; Wu J. Q.; Yao H. Eur. J. Med. Chem. 2023, 250, 115195.

Compd.	IC₅₀/(mmol•L^－1)	Compd.	IC₅₀/(mmol•L^－1)
1a	>70	6a	18.97
1b	>70	6b	39.51
1c	>70	6c	>70
1d	7.11	6d	>70
1e	5.34	6e	1.71
1f	1.05	6f	1.08
1g	11.34	6g	1.53
1h	>70	6h	1.38
1i	2.04	6i	>70
1j	8.07	6j	1.58
1k	>70	6k	>70
1l	>70	6l	>70
1m	7.02	6m	>70
1n	110.50	Fudosteine	8.43

Compd.	IC₅₀/(mmol•L^－1)	Compd.	IC₅₀/(mmol•L^－1)
1a	>70	6a	18.97
1b	>70	6b	39.51
1c	>70	6c	>70
1d	7.11	6d	>70
1e	5.34	6e	1.71
1f	1.05	6f	1.08
1g	11.34	6g	1.53
1h	>70	6h	1.38
1i	2.04	6i	>70
1j	8.07	6j	1.58
1k	>70	6k	>70
1l	>70	6l	>70
1m	7.02	6m	>70
1n	110.50	Fudosteine	8.43

Compd.	IC₅₀/(mg•mL^－1)	Compd.	IC₅₀/(mg•mL^－1)
1a	8.157	6a	2.692
1b	5.160	6c	3.473
1c	2.176	6d	4.314
1d	1.689	6e	1.910
1e	2.960	6f	0.4976
1f	1.439	6g	1.009
1g	0.320	6h	0.01264
1h	15.85	6i	0.2314
1i	3.889	6j	0.003697
1j	0.9764	6k	1.138
1k	2.137	6l	0.9286
1l	37.2	6m	0.5969
1m	6.212	Fudosteine	52.32

Compd.	IC₅₀/(mg•mL^－1)	Compd.	IC₅₀/(mg•mL^－1)
1a	8.157	6a	2.692
1b	5.160	6c	3.473
1c	2.176	6d	4.314
1d	1.689	6e	1.910
1e	2.960	6f	0.4976
1f	1.439	6g	1.009
1g	0.320	6h	0.01264
1h	15.85	6i	0.2314
1i	3.889	6j	0.003697
1j	0.9764	6k	1.138
1k	2.137	6l	0.9286
1l	37.2	6m	0.5969
1m	6.212	Fudosteine	52.32

Compd.	Inhibitory rate/%
Compd.	1 μmol•L^－1	0.1 μmol•L^－1
1a	7.08	1.93
1b	4.08	4.08
1c	3.00	2.15
1d	6.86	－1.07
1e	10.94	3.22
1f	15.44	2.15
1g	7.29	－1.29
1h	9.44	－1.29
1i	2.79	2.36
1j	3.65	2.57
1k	3.65	0.86
1l	7.94	0
1m	2.57	－1.50
Fudosteine	3.65	8.58

慢性呼吸系统疾病药物福多司坦衍生物的设计、合成及活性评价

Design, Synthesis, and Activity Assessment of Fudosteine Derivatives for Chronic Respiratory Disorders

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