Semicarbazides Carrying Indole Core: Synthesis, Cytotoxicity Evaluation against Human Breast Cancer Cell Lines, and Molecular Modeling Studies

In this article, we report the synthesis and cytotoxicity evaluation of novel indole‐carrying semicarbazide derivatives (IS1‐IS15). The target molecules were obtained by the reaction of aryl/alkyl isocyanates with 1H‐indole‐2‐carbohydrazide that was in‐house synthesized from 1H‐indole‐2‐carboxylic a...

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Bibliographic Details
Published in:Chemistry & biodiversity 2023-08, Vol.20 (8), p.e202300609-n/a
Main Authors: Çelik, Beyza, Buran Uğur, Sümeyye, Baran, Münevver, Gündüz, Miyase Gözde, Keskin, Selbi, Önder, Gözde Özge, Bitgen, Nazmiye, Kaya, Serdal, Doğan, Şengül Dilem
Format: Article
Language:English
Subjects:
acylsemicarbazide
antiproliferative
Antiproliferatives
Antitumor agents
Apoptosis
Breast cancer
cancer
Carbonyl compounds
Carbonyls
Carboxylic acids
Cytotoxicity
docking
Drug development
Hydrazine
Hydrazines
Indoles
Isocyanates
Lipophilic
Molecular docking
Molecular modelling
nitrogen heterocycles
NMR
Nuclear magnetic resonance
Semicarbazide
Structural analysis
Synthesis
Toxicity
Tubulin
Tumor cell lines
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Summary:In this article, we report the synthesis and cytotoxicity evaluation of novel indole‐carrying semicarbazide derivatives (IS1‐IS15). The target molecules were obtained by the reaction of aryl/alkyl isocyanates with 1H‐indole‐2‐carbohydrazide that was in‐house synthesized from 1H‐indole‐2‐carboxylic acid. Following structural characterization by 1H‐NMR, 13C‐NMR, and HR‐MS, IS1‐IS15 were investigated for their cytotoxic activity against human breast cancer cell lines, MCF‐7 and MDA‐MB‐231. According to the data obtained from the MTT assay, phenyl ring with a lipophilic group at its para‐position and alkyl moiety were preferential substituents on the indole‐semicarbazide scaffold for antiproliferative activity. The effect of IS12 (N‐(4‐chloro‐3‐(trifluoromethyl)phenyl)‐2‐(1H‐indole‐2‐carbonyl)hydrazine‐1‐carboxamide), the compound that demonstrated remarkable antiproliferative activity on both cell lines, was also evaluated on the apoptotic pathway. Moreover, the calculation of critical descriptors constituting drug‐likeness confirmed the position of the selected compounds in the anticancer drug development process. Finally, molecular docking studies suggested the inhibition of tubulin polymerization as the potential activity mechanism of this class of molecules.
ISSN:1612-1872
1612-1880
1612-1880
DOI:10.1002/cbdv.202300609