Publication: Synthesis, cytotoxicity and QSAR study of N-tosyl-1,2,3,4- tetrahydroisoquinoline derivatives
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0
Issued Date
2013
Resource Type
File Type
application/pdf
ISSN
2536269
Other identifier(s)
2-s2.0-84884209513
Rights Holder(s)
Scopus
Bibliographic Citation
Archives of Pharmacal Research. Vol 36, No.9 (2013), p.1066-1077
Suggested Citation
Pingaew R., Worachartcheewan A., Nantasenamat C., Prachayasittikul S., Ruchirawat S., Prachayasittikul V. Synthesis, cytotoxicity and QSAR study of N-tosyl-1,2,3,4- tetrahydroisoquinoline derivatives. Archives of Pharmacal Research. Vol 36, No.9 (2013), p.1066-1077. doi:10.1007/s12272-013-0111-9 Retrieved from: https://hdl.handle.net/20.500.14740/6569
Abstract
1-Substituted-N-tosyl-1,2,3,4-tetrahydroisoquinoline analogs (4a-4l) were synthesized using the modified Pictet-Spengler reaction and evaluated for cytotoxicity. All tetrahydroisoquinolines displayed cytotoxicity against MOLT-3 cell lines, except for p-methoxy analog 4d. Interestingly, the o-hydroxy derivative 4k was shown to be the most potent cytotoxic against HuCCA-1, A-549 and MOLT-3 cell lines. The lowest IC50 value of 1.23 μM was observed for MOLT-3 cells. Trimethoxy analog 4f exerted the most potent activity against HepG2 with an IC50 of 22.70 μM, which is lower than the reference drug, etoposide. QSAR studies showed that total symmetry index (Gu), 3D-MoRSE (Mor31v and Mor32u) and 3D Petitjean index (PJI3) were the most important descriptors accounting for the observed cytotoxicities. The most potent cytotoxic compound (4k) against MOLT-3 had the highest Gu value, correspondingly the inactive p-methoxy analog (4d) had the lowest Gu value. On the other hand, the highest molecular mass compound (4f) was shown to be the most potent cytotoxic against HepG2 cells. The studies disclose that tetrahydroisoquinolines 4f and 4k are potentially interesting lead pharmacophores that should be further explored. The QSAR models provided insights into the physicochemical properties of the investigated compounds. © 2013 The Pharmaceutical Society of Korea.
Subject(s)
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (2 hydroxyphenyl)isoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (3 hydroxy 4 methoxyphenyl)isoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (3,4,5 trimethoxyphenyl)isoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (4 bromophenyl)isoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (4 hydroxy 3 methoxyphenyl)isoquinolone
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (4 hydroxy 3,5 dimethoxyphenyl)isoquinolone
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (4 hydroxyphenyl)isoquinolone
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (4 methoxyphenyl)isoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 methylisoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 ohenylisoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl]isoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4methylphenyl)sulfonyl] 1 (3 pyridyl)isoquinoline
Doxorubicin
Etoposide
N tosyl 1,2,3,4 tetrahydroisoquinoline derivative
Tetrahydroisoquinoline derivative
Unclassified drug
Article
Bile duct carcinoma
Cancer cell culture
Cell strain HepG2
Controlled study
Drug cytotoxicity
Drug inhibition
Drug synthesis
Human
Human cell
Human cell culture
IC 50
Liver cell carcinoma
Lung carcinoma
Lymphatic leukemia
Molecular weight
Pharmacophore
Physical chemistry
Pictet Spengler reaction
Quantitative structure activity relation
Antineoplastic Agents
Cell Line, Tumor
Cell Proliferation
Cell Survival
Drug Design
Drugs, Investigational
Humans
Hydroxylation
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy
Mass Spectrometry
Molecular Structure
Neoplasms
Physicochemical Phenomena
Quantitative Structure-Activity Relationship
Spectroscopy, Fourier Transform Infrared
Tetrahydroisoquinolines
Tosyl Compounds
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (3 hydroxy 4 methoxyphenyl)isoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (3,4,5 trimethoxyphenyl)isoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (4 bromophenyl)isoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (4 hydroxy 3 methoxyphenyl)isoquinolone
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (4 hydroxy 3,5 dimethoxyphenyl)isoquinolone
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (4 hydroxyphenyl)isoquinolone
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 (4 methoxyphenyl)isoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 methylisoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl] 1 ohenylisoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4 methylphenyl)sulfonyl]isoquinoline
1,2,3,4 tetrahydro 6,7 dimethoxy 2 [(4methylphenyl)sulfonyl] 1 (3 pyridyl)isoquinoline
Doxorubicin
Etoposide
N tosyl 1,2,3,4 tetrahydroisoquinoline derivative
Tetrahydroisoquinoline derivative
Unclassified drug
Article
Bile duct carcinoma
Cancer cell culture
Cell strain HepG2
Controlled study
Drug cytotoxicity
Drug inhibition
Drug synthesis
Human
Human cell
Human cell culture
IC 50
Liver cell carcinoma
Lung carcinoma
Lymphatic leukemia
Molecular weight
Pharmacophore
Physical chemistry
Pictet Spengler reaction
Quantitative structure activity relation
Antineoplastic Agents
Cell Line, Tumor
Cell Proliferation
Cell Survival
Drug Design
Drugs, Investigational
Humans
Hydroxylation
Inhibitory Concentration 50
Magnetic Resonance Spectroscopy
Mass Spectrometry
Molecular Structure
Neoplasms
Physicochemical Phenomena
Quantitative Structure-Activity Relationship
Spectroscopy, Fourier Transform Infrared
Tetrahydroisoquinolines
Tosyl Compounds