Citation: Qi-Chun DING, Yi-Min CAI, Si-Lei WANG, Pei-Pao YAO, Ru-Ya YANG. Exploration of a Library of Triazolothiadiazines as Potent Plant Growth Promoters: Design, Synthesis, X-ray Diffraction Analysis and Bioactivity Studies[J]. Chinese Journal of Structural Chemistry, ;2021, 40(8): 1098-1106. doi: 10.14102/j.cnki.0254–5861.2011–3225 shu

Exploration of a Library of Triazolothiadiazines as Potent Plant Growth Promoters: Design, Synthesis, X-ray Diffraction Analysis and Bioactivity Studies

Department of Pharmacy, Zhangzhou Health Vocational College, Zhangzhou 363000, China

Corresponding author: Qi-Chun DING, 177426824@qq.com
Received Date: 9 April 2021
Accepted Date: 25 June 2021

Fund Project: the Education Research Project of Fujian Province, China JZ180850

Figures(4)

A series of novel 3-methyl-6-aryl-7-aroyl-6, 7-dihydro-5H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazines were designed, synthesized and tested for their antiproliferative activity against HepG2 cell lines in vitro by the standard SRB assay and plant growth regulation activities on wheat (amonocotyledon) and radish (adicotyledon). The results indicated all the title compounds exhibited a very weak antiproliferative activity against HepG2 cell lines in vitro unexpectedly, while showed potent plant growth-regulating activities on both wheat and radish. The crystal structure of trans-4d was obtained from X-ray diffraction: C₁₈H₁₃N₄OSCl₃, M_r = 439.75, monoclinic system, space group P2₁/n, a = 5.3224(7), b = 14.3578(18), c = 24.442(3) Å, β = 94.180(2)°, V = 1862.8(4) Å³, F(000) = 899, Z = 4, D_c = 1.5679 g/cm³, λ = 0.71073 Å, μ = 0.621 mm^-1 and the final R = 0.0382 for 3274 unique reflections with 2851 observed ones (I > 2σ(I)).
- synthesis,
- 1, 2, 4-triazole,
- triazolothiadiazine,
- crystal structure,
- antiproliferative,
- plant growth regulation,
- bioactivity
1. [1]
  Gavara, L.; Verdirosa, F.; Legru, A.; Mercuri, P. S.; Nauton, L.; Sevaille, L.; Feller, G.; Berthomieu, D.; Sannio, F.; Marcoccia, F.; Tanfoni, S.; Luca, F. D.; Gresh, N.; Galleni, M.; Docquier, J. D.; Hernandez, J. F. 4-(N-Alkyl- and -acyl-amino)-1, 2, 4-triazole-3-thione analogs as metallo-β-lactamase inhibitors: impact of 4-linker on potency and spectrum of inhibition. Biomol. 2020, 10, 1094–1111.
2. [2]
  Salah, K. B. H.; Maingot, M.; Blayo, A. L.; M'Kadmi, C.; Damian, M.; Mary, S.; Cantel, S.; Neasta, J.; Oiry, C.; Péraldi-Roux, S.; Fernandez, G.; Romero, G. G.; Perello, M.; Marie, J.; Banères, J. L.; Fehrentz, J. A.; Denoyelle, S. Development of non-peptidic inverse agonists of the ghrelin receptor (GHSR) based on the 1, 2, 4-triazole scaffold. J. Med. Chem. 2020, 63, 10796–10815. doi: 10.1021/acs.jmedchem.9b02122
3. [3]
  Pagniez, F.; Lebouvier, N.; Na, Y. M.; Ourliac-Garnier, I.; Picot, C.; Borgne, M. L.; Pape, P. L. Biological exploration of a novel 1, 2, 4-triazole-indole hybrid molecule as antifungal agent. J. Enzyme Inhib. Med. Chem. 2020, 35, 398–403. doi: 10.1080/14756366.2019.1705292
4. [4]
  Cheng, Y. N.; Jiang, Z. H.; Sun, L. S.; Su, Z. Y.; Zhang, M. M.; Li, H. L. Synthesis of 1, 2, 4-triazole benzoyl arylamine derivatives and their high antifungal activities. Eur. J. Med. Chem. 2020, 200, 112463–112473. doi: 10.1016/j.ejmech.2020.112463
5. [5]
  Shi, J.; Ding, M. H.; Luo, N.; Wan, S. R.; Li, P. J.; Li, J. H.; Bao, X. P. Design, synthesis, crystal structure, and antimicrobial evaluation of 6-fluoroquinazolinylpiperidinyl-containing 1, 2, 4-triazole mannich base derivatives against phytopathogenic bacteria and fungi. J. Agric. Food Chem. 2020, 68, 9613–9623. doi: 10.1021/acs.jafc.0c01365
6. [6]
  Stingaci, E.; Zveaghinteva, M.; Pogrebnoia, S.; Lupascu, L.; Valica, V.; Uncu, L.; Smetanscaia, A.; Drumea, M.; Petrou, A.; Ciric, A.; Glamoclija, J.; Sokovic, M.; Kravtsov, V.; Geronikaki, A.; Macaev, F. New vinyl-1, 2, 4-triazole derivatives as antimicrobial agents: synthesis, biological evaluation and molecular docking studies. Bioorg. Med. Chem. Lett. 2020, 30, 127368–127374. doi: 10.1016/j.bmcl.2020.127368
7. [7]
  Ma, W. F.; Chen, P.; Huo, X. S.; Ma, Y. F.; Li, Y. H.; Diao, P. C.; Yang, F.; Zheng, S. Q.; Hu, M. J.; You, W. W.; Zhao, P. L. Development of triazolothiadiazine derivatives as highly potent tubulin polymerization inhibitors: structure-activity relationship, in vitro and in vivo study. Eur. J. Med. Chem. 2020, 208, 112847–112861. doi: 10.1016/j.ejmech.2020.112847
8. [8]
  Li, Z. Q.; Bai, X. G.; Deng, Q.; Zhang, G. N.; Zhou, L.; Liu, Y. S.; Wang, J. X.; Wang, Y. C. Preliminary SAR and biological evaluation of antitubercular triazolothiadiazine derivatives against drug-susceptible and drugresistant Mtb strains. Bioorg. Med. Chem. 2017, 25, 213–220. doi: 10.1016/j.bmc.2016.10.027
9. [9]
  Winton, V. J.; Aldrich, C.; Kiessling, L. L. Carboxylate surrogates enhance the antimycobacterial activity of UDP-galactopyranose mutase probes. ACS Infect. Dis. 2016, 2, 538–543. doi: 10.1021/acsinfecdis.6b00021
10. [10]
  Khan, I.; Bakht, S. M.; Ibrar, A.; Abbas, S.; Hameed, S.; White, J. M.; Rana, U. A.; Zaib, S.; Shahid, M.; Iqbal, J. Exploration of a library of triazolothiadiazole and triazolothiadiazine compounds as a highly potent and selective family of cholinesterase and monoamine oxidase inhibitors: design, synthesis, X-ray diffraction analysis and molecular docking studies. RSC Adv. 2015, 5, 21249–21267. doi: 10.1039/C5RA00906E
11. [11]
  Alafeefy, A. M.; Abdel-Aziz, H. A.; Vullo, D.; Al-Tamimi, A. M. S.; Awaad, A. S.; Mohamed, M. A.; Capasso, C.; Supuran, C. T. Inhibition of human carbonic anhydrase isozymes I, II, IX and XII with a new series of sulfonamides incorporating aroylhydrazone-, [1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazinyl- or 2-(cyanophenylmethylene)-1, 3, 4-thiadiazol-3(2H)-yl moieties. J. Enzyme Inhib. Med. Chem. 2015, 30, 52–56. doi: 10.3109/14756366.2013.877897
12. [12]
  Zhang, B.; Li, Y. H.; Liu, Y.; Chen, Y. R.; Pan, E. S.; You, W. W.; Zhao, P. L. Design, synthesis and biological evaluation of novel 1, 2, 4-triazolo[3, 4-b][1, 3, 4] thiadiazines bearing furan and thiophene nucleus. Eur. J. Med. Chem. 2015, 103, 335–342. doi: 10.1016/j.ejmech.2015.08.053
13. [13]
  Ding, Q. C.; Zou, Y. H.; Li, Q. L.; Huang, J. J.; Zhang, L. X.; Yin, H. Y. Synthesis, crystal structure and biological activities of phenyl(6-phenyl-3-p-tolyl-6, 7-dihydro-5H-[1, 2, 4]triazolo[3, 4-b][1, 3, 4]thiadiazin-7-yl)methanone. Chin. J. Struct. Chem. 2020, 39, 1531–1538.
14. [14]
  Salam, H. A. A. E.; Yakout, E. S. M. A.; Nawwar, G. A. M.; El-Hashash, M. A.; Mossa, A. T. H. Synthesis of some new 1, 2, 4-triazoles containing olyl moiety and evaluation of their antimicrobial and antioxidant activities. Monatsh. Chem. 2017, 148, 291–304. doi: 10.1007/s00706-016-1751-5
15. [15]
  Ahmad, A.; Varshney, H.; Rauf, A.; Sherwani, A.; Owais, M. Synthesis and anticancer activity of long chain substituted 1, 3, 4-oxadiazol-2-thione, 1, 2, 4-triazol-3-thione and 1, 2, 4-triazolo[3, 4-b]-1, 3, 4-thiadiazine derivatives. Arab. J. Chem. 2014, 10, S3347–S3357.
16. [16]
  Dabholkar, V. V.; Patil, S. R.; Pandey, R. V. Dimethylformamide catalyzed synthesis of novel heterocycles—their characterization and antimicrobial evaluation. J. Heterocyclic Chem. 2013, 50, 403–407. doi: 10.1002/jhet.1073
17. [17]
  Olson, M. E.; Li, M.; Harris, R. S.; Harki, D. A. Small-molecule APOBEC3G DNA cytosine deaminase inhibitors based on a 4-amino-1, 2, 4-triazole-3-thiol scaffold. ChemMedChem. 2013, 8, 112–117. doi: 10.1002/cmdc.201200411
18. [18]
  Bakavoli, M.; Seyedi, S. M.; Shiri, A.; Saberi, S.; Gholami, M.; Sadeghian, H. Synthesis of new derivatives of pyrimido[5, 4-e] [1, 2, 4] triazolo-[3, 4-b][1, 3, 4] thiadiazine and their enzyme inhibitory activity assessment on soybean 15-lipoxygenase. J. Chem. Res. 2013, 37, 48–50. doi: 10.3184/174751912X13549029453945
19. [19]
  Pundeer, R.; Kiran, V.; Prakash, R.; Sushma; Bhatia, S. C.; Sharma, C.; Aneja, K. R. α, α-Dibromoacetophenones mediated synthesis of some new 7H-7-alkoxy-3-alkyl/phenyl-6-aryl-s-triazolo[3, 4-b][1, 3, 4] thiadiazines and their antimicrobial evaluation. Med. Chem. Res. 2012, 21, 4043–4052. doi: 10.1007/s00044-011-9945-1
20. [20]
  Iradyan, M. A.; Iradyan, N. S.; Paronikyan, R. V.; Stepanyan, G. M. Synthesis and biological activity of substituted 6-alkyl(6H)-3-phenyl-1, 2, 4-triazolo[3, 4-b]-1, 3, 4-thiadiazines. Pharm. Chem. J. 2010, 44, 413–417. doi: 10.1007/s11094-010-0479-5
21. [21]
  Bourhis, L. J.; Dolomanov, O. V.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. The anatomy of a comprehensive constrained, restrained refinement program for the modern computing environment – Olex2 dissected. Acta Cryst. 2015, A71, 59–75.
22. [22]
  Zhou, S. N.; Zhang, L. X.; Wu, X. H.; Tian, Y. J.; Liu, L. Q.; Pan, B.; Luo, Y. F.; Shi, M. R. Synthesis and plant growth regulating effects of novel 6-aryl-3-(5-hydroxypentyl)-7-1, 2, 4-trazole[3, 4-b][1, 3, 4]thiadiazines. Chin. J. Synth. Chem. 2019, 27, 19–24.
23. [23]
  Ding, Q. C.; Zhang, L. X.; Zhang, H. L. Synthesis and biological activities of some novel triazolothiadiazines and Schiff bases derived from 4-amino-3-(4-hydroxyphenyl)-1H-1, 2, 4-triazole-5(4H)-thione. Phosphorus, Sulfur Silicon Relat. Elem. 2010, 185, 567–572. doi: 10.1080/10426500902848393
24. [24]
  Zhou, S. N.; Zhang, L. X.; Jin, J. Y.; Zhang, A. J.; Lei, X. X.; Lin, J. S.; He, J. W.; Zhang, H. L. Synthesis and biological activities of some novel triazolothiadiazines and Schiff bases derived from 1, 2, 4-triazole. Phosphorus, Sulfur Silicon Relat. Elem. 2007, 182, 419–432. doi: 10.1080/10426500600976884
25. [25]
  Jin, J. Y.; Zhang, L. X.; Chen, X. X.; Zhang, A. J.; Zhang, H. L. Syntheses and biological activities of 6-aryl-3-(3-hydroxy-propyl)-7H-1, 2, 4-triazolo[3, 4-b][1, 3, 4]thiadiazines. Molecules 2007, 12, 297–303. doi: 10.3390/12030297
1. [1]
  Chao LIU , Jiang WU , Zhaolei JIN . Synthesis, crystal structures, and antibacterial activities of two zinc(Ⅱ) complexes bearing 5-phenyl-1H-pyrazole group. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1986-1994. doi: 10.11862/CJIC.20240153
2. [2]
  Yao HUANG , Yingshu WU , Zhichun BAO , Yue HUANG , Shangfeng TANG , Ruixue LIU , Yancheng LIU , Hong LIANG . Copper complexes of anthrahydrazone bearing pyridyl side chain: Synthesis, crystal structure, anticancer activity, and DNA binding. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 213-224. doi: 10.11862/CJIC.20240359
3. [3]
  Lu LIU , Huijie WANG , Haitong WANG , Ying LI . Crystal structure of a two-dimensional Cd(Ⅱ) complex and its fluorescence recognition of p-nitrophenol, tetracycline, 2, 6-dichloro-4-nitroaniline. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1180-1188. doi: 10.11862/CJIC.20230489
4. [4]
  Lulu DONG , Jie LIU , Hua YANG , Yupei FU , Hongli LIU , Xiaoli CHEN , Huali CUI , Lin LIU , Jijiang WANG . Synthesis, crystal structure, and fluorescence properties of Cd-based complex with pcu topology. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 809-820. doi: 10.11862/CJIC.20240171
5. [5]
  Xiaoxia WANG , Ya'nan GUO , Feng SU , Chun HAN , Long SUN . Synthesis, structure, and electrocatalytic oxygen reduction reaction properties of metal antimony-based chalcogenide clusters. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1201-1208. doi: 10.11862/CJIC.20230478
6. [6]
  Xiaoling WANG , Hongwu ZHANG , Daofu LIU . Synthesis, structure, and magnetic property of a cobalt(Ⅱ) complex based on pyridyl-substituted imino nitroxide radical. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 407-412. doi: 10.11862/CJIC.20240214
7. [7]
  Kaimin WANG , Xiong GU , Na DENG , Hongmei YU , Yanqin YE , Yulu MA . Synthesis, structure, fluorescence properties, and Hirshfeld surface analysis of three Zn(Ⅱ)/Cu(Ⅱ) complexes based on 5-(dimethylamino) isophthalic acid. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1397-1408. doi: 10.11862/CJIC.20240009
8. [8]
  Jia JI , Zhaoyang GUO , Wenni LEI , Jiawei ZHENG , Haorong QIN , Jiahong YAN , Yinling HOU , Xiaoyan XIN , Wenmin WANG . Two dinuclear Gd(Ⅲ)-based complexes constructed by a multidentate diacylhydrazone ligand: Crystal structure, magnetocaloric effect, and biological activity. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 761-772. doi: 10.11862/CJIC.20240344
9. [9]
  Ruikui YAN , Xiaoli CHEN , Miao CAI , Jing REN , Huali CUI , Hua YANG , Jijiang WANG . Design, synthesis, and fluorescence sensing performance of highly sensitive and multi-response lanthanide metal-organic frameworks. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 834-848. doi: 10.11862/CJIC.20230301
10. [10]
  Yinling HOU , Jia JI , Hong YU , Xiaoyun BIAN , Xiaofen GUAN , Jing QIU , Shuyi REN , Ming FANG . A rhombic Dy₄-based complex showing remarkable single-molecule magnet behavior. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 605-612. doi: 10.11862/CJIC.20240251
11. [11]
  Meirong HAN , Xiaoyang WEI , Sisi FENG , Yuting BAI . A zinc-based metal-organic framework for fluorescence detection of trace Cu²⁺. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1603-1614. doi: 10.11862/CJIC.20240150
12. [12]
  Xiumei LI , Yanju HUANG , Bo LIU , Yaru PAN . Syntheses, crystal structures, and quantum chemistry calculation of two Ni(Ⅱ) coordination polymers. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 2031-2039. doi: 10.11862/CJIC.20240109
13. [13]
  Xiumei LI , Linlin LI , Bo LIU , Yaru PAN . Syntheses, crystal structures, and characterizations of two cadmium(Ⅱ) coordination polymers. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 613-623. doi: 10.11862/CJIC.20240273
14. [14]
  Yan XU , Suzhi LI , Yan LI , Lushun FENG , Wentao SUN , Xinxing LI . Structure variation of cadmium naphthalene-diphosphonates with the changing rigidity of N-donor auxiliary ligands. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 395-406. doi: 10.11862/CJIC.20240226
15. [15]
  Xinting XIONG , Zhiqiang XIONG , Panlei XIAO , Xuliang NIE , Xiuying SONG , Xiuguang YI . Synthesis, crystal structures, Hirshfeld surface analysis, and antifungal activity of two complexes Na(Ⅰ)/Cd(Ⅱ) assembled by 5-bromo-2-hydroxybenzoic acid ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1661-1670. doi: 10.11862/CJIC.20240145
16. [16]
  Jing WU , Puzhen HUI , Huilin ZHENG , Pingchuan YUAN , Chunfei WANG , Hui WANG , Xiaoxia GU . Synthesis, crystal structures, and antitumor activities of transition metal complexes incorporating a naphthol-aldehyde Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2422-2428. doi: 10.11862/CJIC.20240278
17. [17]
  Huan ZHANG , Jijiang WANG , Guang FAN , Long TANG , Erlin YUE , Chao BAI , Xiao WANG , Yuqi ZHANG . A highly stable cadmium(Ⅱ) metal-organic framework for detecting tetracycline and p-nitrophenol. Chinese Journal of Inorganic Chemistry, 2024, 40(3): 646-654. doi: 10.11862/CJIC.20230291
18. [18]
  Shuyan ZHAO . Field-induced Co^Ⅱ single-ion magnet with pentagonal bipyramidal configuration. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1583-1591. doi: 10.11862/CJIC.20240231
19. [19]
  Zhaodong WANG . In situ synthesis, crystal structure, and magnetic characterization of a trinuclear copper complex based on a multi-substituted imidazo[1,5-a]pyrazine scaffold. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 597-604. doi: 10.11862/CJIC.20240268
20. [20]
  Xiaofen GUAN , Yating LIU , Jia LI , Yiwen HU , Haiyuan DING , Yuanjing SHI , Zhiqiang WANG , Wenmin WANG . Synthesis, crystal structure, and DNA-binding of binuclear lanthanide complexes based on a multidentate Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2486-2496. doi: 10.11862/CJIC.20240122

Get Citation

PDF

XML

Metrics

PDF Downloads(2)
Abstract views(307)
HTML views(4)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142