Publication: Synthesis, cytotoxicity and QSAR study of N-tosyl-1,2,3,4- tetrahydroisoquinoline derivatives
Issued Date
2013-09-01
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19763786
02536269
02536269
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2-s2.0-84884209513
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Mahidol University
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SCOPUS
Bibliographic Citation
Archives of Pharmacal Research. Vol.36, No.9 (2013), 1066-1077
Suggested Citation
Ratchanok Pingaew, Apilak Worachartcheewan, Chanin Nantasenamat, Supaluk Prachayasittikul, Somsak Ruchirawat, Virapong Prachayasittikul Synthesis, cytotoxicity and QSAR study of N-tosyl-1,2,3,4- tetrahydroisoquinoline derivatives. Archives of Pharmacal Research. Vol.36, No.9 (2013), 1066-1077. doi:10.1007/s12272-013-0111-9 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/31230
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Title
Synthesis, cytotoxicity and QSAR study of N-tosyl-1,2,3,4- tetrahydroisoquinoline derivatives
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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 IC50value of 1.23 μM was observed for MOLT-3 cells. Trimethoxy analog 4f exerted the most potent activity against HepG2 with an IC50of 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.