Synthesis and antibacterial activity of new hybrid derivatives of 5-sulfamoyl-1 H -indole and 4-thiazolidinone groups
- PDF / 816,783 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 107 Downloads / 235 Views
ORIGINAL PAPER
Synthesis and antibacterial activity of new hybrid derivatives of 5‑sulfamoyl‑1H‑indole and 4‑thiazolidinone groups Özlen Güzel‑Akdemir1 · Muhammed Trawally1 · Mehtap Özbek‑Babuç1 · Berna Özbek‑Çelik2 · Görkem Ermut1 · Hakan Özdemir1 Received: 25 April 2020 / Accepted: 15 July 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract The synthesis of a series of new 3-phenyl-5-sulfamoyl-N-(7/8/9-(non)substituted-3-oxo-1-thia-4-azaspiro[4.4]non/[4.5]dec4-yl)-1H-indole-2-carboxamide derivatives and their subsequent testing for antibacterial activity is described in this paper. 4-Sulfamoylbenzenediazonium chloride was synthesized from diazotization of sulfanilamide and sodium nitrite in the presence of HCl and was further allowed to condense with ethyl 2-benzylacetoacetate to produce ethyl 2-benzyl-2-(4-sulfamoylphenyl)hydrazonoacetate. This compound was cyclized to ethyl 5-sulfamoyl-3-phenyl-1H-indole-2-carboxylate employing the Fischer-indole procedure. The reaction of ethyl 5-sulfamoyl-3-phenyl-1H-indole-2-carboxylate with hydrazine hydrate yielded sulfamoyl-3-phenyl-1H-indole-2-carbohydrazide. Through a cyclization process, the spirothiazolidinone derivatives were obtained from the reaction of suitable cyclic ketones with 5-sulfamoyl-3-phenyl-1H-indole-2-carbohydrazide in the presence of thioglycolic acid/thiolactic acid. Structural elucidation of the novel compounds was achieved with the help of UV, IR, 1H NMR, HSQC, ESI–MS, and as well as elemental analysis. Among all the synthesized compounds tested, four compounds displayed the most promising antibacterial activity. The influence of the substituents and their positions on the antibacterial activity was evaluated. Graphic abstract R4 R5
Cyclocondensation
C 6H 5
H2NO2S
NH H2NO2S
H2NO2S NH2
C 6H 5 NH
NHNH2
NH N O
R3 R2 R1
S
R
O
One-pot synthesis
O H2NO2S
C 6H 5
O
O
NH HN N
R S
Keywords One-pot synthesis · Spirothiazolidinones · Pharmacophore hybrid · Antibacterial activity · Spectroscopy
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00706-020-02664-9) contains supplementary material, which is available to authorized users. * Özlen Güzel‑Akdemir [email protected] 1
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Istanbul University, Beyazit, Istanbul, Turkey
Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Istanbul University, Beyazit, Istanbul, Turkey
2
The indole ring is considered a privileged structure and an attractive scaffold for drug discovery. Indoles can bind to different proteins. This gives it a hallmark of being a constituent of many pharmaceutical drugs [1] and thus, it is considered to be one of the most essential heterocyclic structures in drug discovery. Structural diversity with various and promising biological activities can easily be achieved via ring substitution, particularly, substitution on carbon 2 and 5 [2]. Many bioactive compounds such as the endogenous signaling
Data Loading...
