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QSAR Study and Design of Novel Organoselenium and alpha-Tocopherol Derivatives with Enhanced Chemotherapeutic Activity

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2009
Authors
Nikolić, Katarina
Agbaba, Danica
Article (Published version)
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Abstract
Organic selenides, such as Se-alkyl-selenocysteine and derivatives, are active in suppressing chemically induced mammary carcinogenesis in rats. Here the quantitative structure-activity relationship (QSAR) study of ten related alkyl-chalcogens was performed to correlate their structural properties with the measured chemotherapeutic activities (ED(50)). The CS Gaussian 98 program with Hartree-Fock/3-21G (d) basis set was applied for molecular properties computations of the optimized models. Electron Density on chalcogen (ED(X)) expressed the strongest influence on anticancer activity of the examined molecules. Linear regression model of the alkyl-chalcogens, log(ED(50)) = f (ED(X)), was obtained with R(2) = 0.964 and cross-validation parameter q(pre)(2) = 0.950. Synergy between organo-selenides and vitamin E in chemotherapeutic activity led to propose novel organoselenium-alpha-tocopheryl esters as potent anticancer agents. Anticancer activities (log(ED(50))) of the designed alkyl-selen...o/tocopheryl esters (S-1 to S-4) were evaluated using the developed QSAR/alkyl-chalcogens model and the most potent chemotherapeutic agents (ED(50)(S-1): 2.60 ppm and ED(50)(S-4): 2.55 ppm). On the other side, previously created QSAR model for in vitro anticancer activity (IC(50)) for tocopherol derivatives, log(IC(50))= f (NCH(3), logDpH 5.0, O-charge) with R(2)= 0.940 and q(pre)(2)= 0.879, was employed with IC(50) evaluation of the proposed alkyl-seleno/tocopheryl esters (S-1 to S-4). Calculated antiproliferative activities of the designed compounds, IC(50)(S-1): 25.65 mu M and IC(50)(S-4): 31.36 mu M, were significantly stronger than activities of other related anticancer agents, IC(50): 4-1461 mu M.

Keywords:
Alkyl-chalcogens / alpha-tocopherol / Anticancer activity / QSAR / Atomic electron density / Molecular electrostatic potential
Source:
Letters in Drug Design and Discovery, 2009, 6, 3, 228-235
Publisher:
  • Bentham Science Publ Ltd, Sharjah
Funding / projects:
  • Sinteza, kvantitativni odnosi između strukture/osobina i aktivnosti, fizičko-hemijska karakterizacija i analiza farmakološki aktivnih supstanci (RS-142071)

DOI: 10.2174/157018009787847882

ISSN: 1570-1808

WoS: 000265798800011

Scopus: 2-s2.0-64949107623
[ Google Scholar ]
7
7
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/1229
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Nikolić, Katarina
AU  - Agbaba, Danica
PY  - 2009
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1229
AB  - Organic selenides, such as Se-alkyl-selenocysteine and derivatives, are active in suppressing chemically induced mammary carcinogenesis in rats. Here the quantitative structure-activity relationship (QSAR) study of ten related alkyl-chalcogens was performed to correlate their structural properties with the measured chemotherapeutic activities (ED(50)). The CS Gaussian 98 program with Hartree-Fock/3-21G (d) basis set was applied for molecular properties computations of the optimized models. Electron Density on chalcogen (ED(X)) expressed the strongest influence on anticancer activity of the examined molecules. Linear regression model of the alkyl-chalcogens, log(ED(50)) = f (ED(X)), was obtained with R(2) = 0.964 and cross-validation parameter q(pre)(2) = 0.950. Synergy between organo-selenides and vitamin E in chemotherapeutic activity led to propose novel organoselenium-alpha-tocopheryl esters as potent anticancer agents. Anticancer activities (log(ED(50))) of the designed alkyl-seleno/tocopheryl esters (S-1 to S-4) were evaluated using the developed QSAR/alkyl-chalcogens model and the most potent chemotherapeutic agents (ED(50)(S-1): 2.60 ppm and ED(50)(S-4): 2.55 ppm). On the other side, previously created QSAR model for in vitro anticancer activity (IC(50)) for tocopherol derivatives, log(IC(50))= f (NCH(3), logDpH 5.0, O-charge) with R(2)= 0.940 and q(pre)(2)= 0.879, was employed with IC(50) evaluation of the proposed alkyl-seleno/tocopheryl esters (S-1 to S-4). Calculated antiproliferative activities of the designed compounds, IC(50)(S-1): 25.65 mu M and IC(50)(S-4): 31.36 mu M, were significantly stronger than activities of other related anticancer agents, IC(50): 4-1461 mu M.
PB  - Bentham Science Publ Ltd, Sharjah
T2  - Letters in Drug Design and Discovery
T1  - QSAR Study and Design of Novel Organoselenium and alpha-Tocopherol Derivatives with Enhanced Chemotherapeutic Activity
VL  - 6
IS  - 3
SP  - 228
EP  - 235
DO  - 10.2174/157018009787847882
ER  - 
@article{
author = "Nikolić, Katarina and Agbaba, Danica",
year = "2009",
abstract = "Organic selenides, such as Se-alkyl-selenocysteine and derivatives, are active in suppressing chemically induced mammary carcinogenesis in rats. Here the quantitative structure-activity relationship (QSAR) study of ten related alkyl-chalcogens was performed to correlate their structural properties with the measured chemotherapeutic activities (ED(50)). The CS Gaussian 98 program with Hartree-Fock/3-21G (d) basis set was applied for molecular properties computations of the optimized models. Electron Density on chalcogen (ED(X)) expressed the strongest influence on anticancer activity of the examined molecules. Linear regression model of the alkyl-chalcogens, log(ED(50)) = f (ED(X)), was obtained with R(2) = 0.964 and cross-validation parameter q(pre)(2) = 0.950. Synergy between organo-selenides and vitamin E in chemotherapeutic activity led to propose novel organoselenium-alpha-tocopheryl esters as potent anticancer agents. Anticancer activities (log(ED(50))) of the designed alkyl-seleno/tocopheryl esters (S-1 to S-4) were evaluated using the developed QSAR/alkyl-chalcogens model and the most potent chemotherapeutic agents (ED(50)(S-1): 2.60 ppm and ED(50)(S-4): 2.55 ppm). On the other side, previously created QSAR model for in vitro anticancer activity (IC(50)) for tocopherol derivatives, log(IC(50))= f (NCH(3), logDpH 5.0, O-charge) with R(2)= 0.940 and q(pre)(2)= 0.879, was employed with IC(50) evaluation of the proposed alkyl-seleno/tocopheryl esters (S-1 to S-4). Calculated antiproliferative activities of the designed compounds, IC(50)(S-1): 25.65 mu M and IC(50)(S-4): 31.36 mu M, were significantly stronger than activities of other related anticancer agents, IC(50): 4-1461 mu M.",
publisher = "Bentham Science Publ Ltd, Sharjah",
journal = "Letters in Drug Design and Discovery",
title = "QSAR Study and Design of Novel Organoselenium and alpha-Tocopherol Derivatives with Enhanced Chemotherapeutic Activity",
volume = "6",
number = "3",
pages = "228-235",
doi = "10.2174/157018009787847882"
}
Nikolić, K.,& Agbaba, D.. (2009). QSAR Study and Design of Novel Organoselenium and alpha-Tocopherol Derivatives with Enhanced Chemotherapeutic Activity. in Letters in Drug Design and Discovery
Bentham Science Publ Ltd, Sharjah., 6(3), 228-235.
https://doi.org/10.2174/157018009787847882
Nikolić K, Agbaba D. QSAR Study and Design of Novel Organoselenium and alpha-Tocopherol Derivatives with Enhanced Chemotherapeutic Activity. in Letters in Drug Design and Discovery. 2009;6(3):228-235.
doi:10.2174/157018009787847882 .
Nikolić, Katarina, Agbaba, Danica, "QSAR Study and Design of Novel Organoselenium and alpha-Tocopherol Derivatives with Enhanced Chemotherapeutic Activity" in Letters in Drug Design and Discovery, 6, no. 3 (2009):228-235,
https://doi.org/10.2174/157018009787847882 . .

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