Three new geldanamycin (GDM) derivatives, 17-((S)-2-amino-3-(1H-indol-3-ylpropan-1-ol)-17- demethoxygeldanamycin (2), 17-((S)-2-amino-3-phenylpropan-1-ol)-17-demethoxygeldanamycin (3), and 17-((S)-4- (2-amino-3-hydroxypropyl)phenol)-17-demethoxygeldanamycin (4), were synthesized by nucleophilic substitution of GDM (1). The binding ability of these compounds at the N-terminal domain of heat shock protein [Protein Data Bank (PDB) ID: 1OSF] derived from the PDB was analyzed by ligand–protein docking. Hydrogen-bonding interactions of compounds 2 and 3 were equal to those of 17-dimethylamino-ethylamino-17-demethoxygeldanamycin (17-DMAG), with binding energies of âˆ’98.33 and âˆ’122.41 kcal/mol, respectively. The solubility of the synthesized compounds was ascertained. The solubilities of compounds 2, 3, and 4 in water were 5.571 mM, 1.963 mM, and 1.918 mM, higher than that of compound 1 by approximately 36.65, 12.91, and 12.62 times, respectively. The cytotoxicity activity of the synthesized compounds was also evaluated against cancer cell lines using a tetrazolium-based colorimetric assay. These compounds showed high anticancer activity against human cervical carcinoma cells cells, with inhibitory concentration (IC50) values in the range of 19.36–45.66 µg/ml, which were better than that of compound 1, with IC50 values of 110.46 µg/ml. Compound 3 also exhibited cytotoxic activity against human hepatocellular carcinoma cells cells, with an IC50 value of 24.62 µg/ml. These compounds were less active against MDA-MB-231 cells, compared with compound 1. Compound 2 also showed weak cytotoxic activity on Vero and LLC-MK2 cells, with IC50 values of 229.19 and 330.58 µg/ml, respectively. The predicted results indicated that these compounds have similar absorption, distribution, metabolism, excretion, and toxicity () parameters as well as structures predictive of hepatotoxicity. The results showed that some of the synthesized compounds revealed selective cytotoxicity toward some cancer cells. Therefore, further studies on the synthesized compounds could be helpful in the treatment of some cancers.
ADMET, Amine-geldanamycin hybrids, Anticancer activity, Cytotoxicity activity, Geldanamycin derivatives, Molecular docking, Solubility.
Improving cell transplantation by understanding and manipulating the phagocytic activity of peripheral glia.
Nazareth L, St John J, Ekberg J
Neural regeneration research. 2022; 17(2): 313-314
Selective detection of enrofloxacin in biological and environmental samples using a molecularly imprinted electrochemiluminescence sensor based on functionalized copper nanoclusters.
Wang D, Jiang S, Liang Y, Wang X, Zhuang X, Tian C, Luan F, Chen L
Talanta. 2022; 236(): 122835
Integrated molecular and affiliation network analysis: Core-periphery social clustering is associated with HIV transmission patterns.
Fujimoto K, Paraskevis D, Kuo JC, Hallmark CJ, Zhao J, Hochi A, Kuhns LM, Hwang LY, Hatzakis A, Schneider JA
Social networks. 2022; 68(): 107-117
In Silico Analysis of Therapeutic Antibody Aggregation and the Influence of Glycosylation.
Jeon H, Hayes JM, Mok KH
Methods in molecular biology (Clifton, N.J.). 2022; 2370(): 169-183
Rapid Antibody Glycoengineering in CHO Cells Via RNA Interference and CGE-LIF N-Glycomics.
Kotidis P, Marbiah M, Donini R, GÃ³mez IA, Del Val IJ, Haslam SM, Polizzi KM, Kontoravdi C
Methods in molecular biology (Clifton, N.J.). 2022; 2370(): 147-167