Synthesis,pharmacological evaluation,and molecular modeling studies of novel isatin hybrids as potential anticancer agents |
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Affiliation: | 1. Department of Pharmaceutical Chemistry, Arulmigu Kalasalingam College of Pharmacy, Krishnankovil- 626126, Tamilnadu, India;2. Department of Pharmacology, College of Pharmacy, King Khalid University, P. O. Box: 960, Abha 61421, Saudi Arabia;3. Faculty of Pharmacy, Philadelphia University, P.O. Box 1, Amman, 19392, Jordan;4. Department of Pharmaceutical Technology, Division of Pharmaceutical Chemistry, Jadavpur University, Kolkata 700032, India;5. Department of Microbiology & Clinical Parasitology, College of Medicine, King Khalid, University, Al-Qara, Saudi Arabia;6. Center for Stem Cell Research, College of Medicine, King Khalid University, Al-Qara, Saudi Arabia |
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Abstract: | A novel series of isatin hybrids 5a-g was designed, synthesized, and characterized spectroscopically. The synthesized compounds were evaluated for their cytotoxic activity against the human breast cancer cell line (MCF-7) by in vitro MTT assay. Amongst the tested compounds, 5e compound bearing benzyl moiety at N4 piperazine was found to be the most active with the promising IC50 (12.47 µM). Moreover, the active compounds 5e and 5g were subjected to antitumor evaluation (in vivo) against Dalton’s ascitic lymphoma (DAL) cell line and the results suggested that the best active compound 5e can normalize the blood picture in comparison to the standard drug. An in silico molecular docking study using the crystal structure of Hsp90 protein described the role of significant protein–ligand interactions and revealed more insights into the binding mode. The drug-likeliness of the compounds was predicted based on Lipinski's rule of five and pharmacokinetic ADME parameters. Hence, the synthesized isatin hybrids could be novel starting point anticancer lead compounds demonstrating drug-like properties which can be explored further for anticancer drug discovery. |
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Keywords: | Isatin-pyrimidine hybrid Antiproliferative activity Breast cancer cell (MCF-7) Dalton’s ascitic lymphoma (DAL) Molecular docking ADME" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" absorption distribution metabolism and excretion ANOVA" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" analysis of variance DAC" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" dalton’s ascitic lymphoma DHFR" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" dihydrofolate reductase DMF" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" dimethylformamide DMSO" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" dimethylsulfoxide DNA" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" deoxyribonucleic acid ESI" },{" #name" :" keyword" ," $" :{" id" :" k0105" }," $$" :[{" #name" :" text" ," _" :" MS, electrospray ionization mass spectrometry 5, FU" },{" #name" :" keyword" ," $" :{" id" :" k0115" }," $$" :[{" #name" :" text" ," _" :" fluorouracil FT, IR" },{" #name" :" keyword" ," $" :{" id" :" k0125" }," $$" :[{" #name" :" text" ," _" :" fourier transform infrared spectroscopy HIA" },{" #name" :" keyword" ," $" :{" id" :" k0135" }," $$" :[{" #name" :" text" ," _" :" Human intestinal absorption Hsp90" },{" #name" :" keyword" ," $" :{" id" :" k0145" }," $$" :[{" #name" :" text" ," _" :" heat shock protein 90 the concentration of drug required for 50% inhibition ILS" },{" #name" :" keyword" ," $" :{" id" :" k0165" }," $$" :[{" #name" :" text" ," _" :" increase in life span KBr" },{" #name" :" keyword" ," $" :{" id" :" k0175" }," $$" :[{" #name" :" text" ," _" :" potassium bromide the median lethal dose MCF" },{" #name" :" keyword" ," $" :{" id" :" k0195" }," $$" :[{" #name" :" text" ," _" :" 7, human breast cancer cell line MST" },{" #name" :" keyword" ," $" :{" id" :" k0205" }," $$" :[{" #name" :" text" ," _" :" median survival time MTT, 3" },{" #name" :" keyword" ," $" :{" id" :" k0215" }," $$" :[{" #name" :" text" ," _" :" (4,5, dimethylthiazol, 2, yl), 2,5, diphenyltetrazolium bromide NMR" },{" #name" :" keyword" ," $" :{" id" :" k0225" }," $$" :[{" #name" :" text" ," _" :" nuclear magnetic resonance PDB" },{" #name" :" keyword" ," $" :{" id" :" k0235" }," $$" :[{" #name" :" text" ," _" :" protein data bank RBC" },{" #name" :" keyword" ," $" :{" id" :" k0245" }," $$" :[{" #name" :" text" ," _" :" red blood cells RNA" },{" #name" :" keyword" ," $" :{" id" :" k0255" }," $$" :[{" #name" :" text" ," _" :" ribonucleic acid SAR" },{" #name" :" keyword" ," $" :{" id" :" k0265" }," $$" :[{" #name" :" text" ," _" :" structure, activity relationship SEM" },{" #name" :" keyword" ," $" :{" id" :" k0275" }," $$" :[{" #name" :" text" ," _" :" standard error of the mean TLC" },{" #name" :" keyword" ," $" :{" id" :" k0285" }," $$" :[{" #name" :" text" ," _" :" thin, layer chromatography TMS" },{" #name" :" keyword" ," $" :{" id" :" k0295" }," $$" :[{" #name" :" text" ," _" :" tetramethylsilane WBC" },{" #name" :" keyword" ," $" :{" id" :" k0305" }," $$" :[{" #name" :" text" ," _" :" white blood cells |
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