QSAR studies of novel iminochromene derivatives as carbonyl reductase 1 (CBR1) inhibitors

Nosrat Maddady; Alireaza Mohadesi Zarandi; Azra Horzadeh

QSAR studies of novel iminochromene derivatives as carbonyl reductase 1 (CBR1) inhibitors

Abstract

A quantitative Structure-Activity Relationship (QSAR) model was applied to the prediction of the activity of iminochromene derivatives. The inhibition activity of 34 carbonyl reductase 1 (CBR1) inhibitors were modeled with the descriptors of quantum-chemical calculations with density functional theory (DFT) method at B3LYP/6‒31G level. This study was conducted using the multiple linear regressions (MLR), the partial least square analysis (PLS) and the principal component analysis (PCA) method. Results displayed that the MLR method predicted of activity good enough. The best model, with seven descriptors was selected. Also it indicates very good consistency towards data variations for the validation methods. The predicted values of activities are in suitable agreement with the experimental results. The obtained results suggested that the PCA method could be more helpful to predict the biological activity of iminochromene derivatives. It is anticipated to be useful to predict the activity of other compounds in the same groups.

Keywords

References

[1] Hoffmann F, Maser E. Carbonyl reductases and pluripotent hydroxysteroid dehydrogenases of the short-chain dehydrogenase/reductase superfamily. Drug Metab Rev. 2007; 39(1): 87-144.
[2] Oppermann U. Carbonyl reductases: the complex relationships of mammalian carbonyl- and quinone-reducing enzymes and their role in physiology. Annu Rev Pharmacol Toxicol. 2007; 47: 293-322.
[3] Malatkova P, Maser E, Wsol V. Human carbonyl reductases. Curr Drug Metab. 2010; 11(8): 639-658.
[4] Wermuth B. Purification and properties of an NADPH-dependent carbonyl reductase from human brain. J Biol Chem. 1981; 256(3): 1206-1213.
[5] Tanaka M, Bateman R, Rauh D, Vaisberg E, Ramachandani S, Zhang C, Hansen KC, et al. An unbiased cell morphology-based screen for new, biologically active small molecules. PLoS Biol. 2005; 3(5): 128-135.
[6] Zimmermann TJ, Niesen FH, Pilka ES, Knapp S, Oppermann U, Maier ME. Discovery of a potent and selective inhibitor for human carbonyl reductase 1. Bioorg Med Chem. 2009; 17(2): 530-536.
[7] Ito Y, Mitani T, Harada N, et al. Identification of carbonyl reductase 1 as a resveratrol-binding protein. J Nutr Sci Vitaminol. (Tokyo) 2013; 59(4): 358-364.
[8] Huang W, Ding L, Huang Q, et al. Carbonyl reductase 1 as a novel target of (-)-epigallocatechin gallate against hepatocellular carcinoma. Hepatology. 2010; 52(2): 703-714.

[9] Gonzalez-Covarrubias V, Kalabus JL, Blanco JG. Inhibition of polymorphic human carbonyl reductase 1 by the flavonoid 7-monohydroxyethyl rutoside. Pharm Res. 2008; 25(7): 1730-1734.
[10] Carlquist M, Frejd T, Gorwa-Grauslund MF. Flavonoids as inhibitors of human carbonyl reductase 1. Chem Biol Interact. 2008; 174(2): 98-108.
[11] Hu D, Miyagi N, Arai Y, et al. Synthesis of 8-hydroxy-2-iminochromene derivatives as selective inhibitors of human carbonyl reductase 1. Org Biomol Chem. 2015; 13(27): 7487-7499.
[12] Hadjipavlou-Litina D. Reevaluation and new results in quantitative structure-activity studies of anticonvulsants. Med Res Rev. 1998; 18(2): 91-119.
[13] Gramatica P, Papa E. QSAR modeling of bioconcentration factor by theoretical molecular descriptors. QSAR Comb Sci. 2003; 22(3): 374-385.
[14] Hansch C, Kurup A, Garg R, Gao H. Chem-bioinformatics and QSAR: a review of QSAR lacking positive hydrophobic terms. Chem Rev. 2001; 101(3): 619-672.
[15] Agrawal VK, Bano S, Supuran CT, Khadikar PV. QSAR study on carbonic anhydrase inhibitors: aromatic/heterocyclic sulfonamides. Eur J Med Chem. 2004; 39(7): 593-600.
[16] Kumar R, Son M, Bavi R, et al. Novel chemical scaffolds of the tumor marker AKR1B10 inhibitors discovered by 3D QSAR pharmacophore modeling. Acta Pharmacol Sin. 2015; 36(8): 998-1012.
[17] Sawant RL, Ramdin SS, Wadekar JB. Synthesis, QSAR and docking studies of 5HT2A receptor antagonising thiazolo[3,2-a]pyrimidines. Marmara Pharm J. 2014; 18(3): 109-119.
[18] Kumar R, Malla P, Verma A, Kumar M. Design of potent human steroid 5α-reductase inhibitors: 3D-QSAR CoMFA, CoMSIA and docking studies. Med Chem Res. 2013; 22(10): 4568-4582.
[19] Chaudhari RY, Bhise SB, Yadav A, Sonawane T. QSAR, Synthesis and Docking Study of 1,4-DHP as Novel Antitubercular Agents. J Pharm Res Clin Pract. 2016; 6(1): 1-9.
[20] Vasanthanathan P, Lakshmi M, Babu MA, Kaskhedikar SG. Classical QSAR study on chromene derivatives as lanosterol 14α-demethylase inhibitors. Med Chem. 2006; 2(4): 363-367.
[21] Firoozpour L, Edraki N, Nakhjiri M, et al. Cytotoxic activity evaluation and QSAR study of chromene-based chalcones. Arch Pharm Res. 2012; 35(12): 2117-2125.
[22] Consonni V, Ballabio D, Todeschini R. Comments on the definition of the Q2 parameter for QSAR validation. J Chem Inf Model. 2009; 49(7): 1669-1678.
[23] Consonni V, Ballabio D, Todeschini R. Evaluation of model predictive ability by external validation techniques. J Chemometrics. 2010; 24(3-4): 194-201.
[24] Lee PY, Chen CY. Toxicity and QSAR of benzoic acids to Pseudokirchneriella subcapitata. J Hazard Mater. 2009; 165(1-3): 156-161.
[25] Jing G, Zhou Z, Zhuo J. QSAR study of toxicity of quaternary ammonium compounds on green algae. Chemosphere. 2012; 86(1): 76-82.
[26] Shi LM, Fang H, Tong W, et al. QSAR models using a large diverse set of estrogens. J Chem Inf Comput Sci. 2001; 41(1): 186-195.
[27] Hawkins DM. The Problem of Overfitting. J Chem Inf Comput Sci. 2004; 44(1): 1-12.
[28] Consonni V, Ballabio D, Todeschini R. Evaluation of model predictive ability by external validation techniques. J Chemometrics. 2010; 24(3-4): 194-201.
[29] Wold S, Ericksson L. Partial least squares projections to latent structures (PLS) in chemistry. In Encyclopedia of Computational Chemistry, Wiley, 2002.
[30] Vaira S, Mantovani VE, Robles JC, et al. Chemometrics: PCA and PCR for the Authentication of Orange Juice. J Anal Lett. 1999; 32(15): 3131-3141.
[31] Frisch MJ. Gaussian 03, Revision B.01, Gaussian, Inc., Pittsburgh, PA, 2003.
[32] Parr RG, Pearson RG. Absolute hardness: companion parameter to absolute electronegativity. J Am Chem Soc. 1983; 105(26): 7512-7516.
[33] Lee C, Yang W, Parr RG. Development of the Colle-Salvetti correlation energy formula into a functional of the electron density. Phys Rev B. 1988; 37(2): 785-789.
[34] Mushinski A, Nightingale MP. Many-body trial wave functions for atomic systems and noble gas clusters. J Chem Phys. 1994; 101(5): 8831-8840.

Details

Primary Language

English

Subjects

Pharmaceutical Chemistry

Journal Section

Research Article

Authors

Nosrat Maddady ^*
Iran

Alireaza Mohadesi Zarandi This is me
Iran

Azra Horzadeh This is me
Iran

Publication Date

June 27, 2025

Submission Date

July 9, 2017

Acceptance Date

November 7, 2017

Published in Issue

Year 2018 Volume: 22 Number: 2

IZ

https://izlik.org/JA84NJ47WM

Cite

RIS / Bibtex

APA

Maddady, N., Zarandi, A. M., & Horzadeh, A. (2025). QSAR studies of novel iminochromene derivatives as carbonyl reductase 1 (CBR1) inhibitors. Journal of Research in Pharmacy, 22(2), 227-236. https://izlik.org/JA84NJ47WM

AMA

1.Maddady N, Zarandi AM, Horzadeh A. QSAR studies of novel iminochromene derivatives as carbonyl reductase 1 (CBR1) inhibitors. J. Res. Pharm. 2025;22(2):227-236. https://izlik.org/JA84NJ47WM

Chicago

Maddady, Nosrat, Alireaza Mohadesi Zarandi, and Azra Horzadeh. 2025. “QSAR Studies of Novel Iminochromene Derivatives As Carbonyl Reductase 1 (CBR1) Inhibitors”. Journal of Research in Pharmacy 22 (2): 227-36. https://izlik.org/JA84NJ47WM.

EndNote

Maddady N, Zarandi AM, Horzadeh A (June 1, 2025) QSAR studies of novel iminochromene derivatives as carbonyl reductase 1 (CBR1) inhibitors. Journal of Research in Pharmacy 22 2 227–236.

IEEE

[1]N. Maddady, A. M. Zarandi, and A. Horzadeh, “QSAR studies of novel iminochromene derivatives as carbonyl reductase 1 (CBR1) inhibitors”, J. Res. Pharm., vol. 22, no. 2, pp. 227–236, June 2025, [Online]. Available: https://izlik.org/JA84NJ47WM

ISNAD

Maddady, Nosrat - Zarandi, Alireaza Mohadesi - Horzadeh, Azra. “QSAR Studies of Novel Iminochromene Derivatives As Carbonyl Reductase 1 (CBR1) Inhibitors”. Journal of Research in Pharmacy 22/2 (June 1, 2025): 227-236. https://izlik.org/JA84NJ47WM.

JAMA

1.Maddady N, Zarandi AM, Horzadeh A. QSAR studies of novel iminochromene derivatives as carbonyl reductase 1 (CBR1) inhibitors. J. Res. Pharm. 2025;22:227–236.

MLA

Maddady, Nosrat, et al. “QSAR Studies of Novel Iminochromene Derivatives As Carbonyl Reductase 1 (CBR1) Inhibitors”. Journal of Research in Pharmacy, vol. 22, no. 2, June 2025, pp. 227-36, https://izlik.org/JA84NJ47WM.

Vancouver

1.Nosrat Maddady, Alireaza Mohadesi Zarandi, Azra Horzadeh. QSAR studies of novel iminochromene derivatives as carbonyl reductase 1 (CBR1) inhibitors. J. Res. Pharm. [Internet]. 2025 Jun. 1;22(2):227-36. Available from: https://izlik.org/JA84NJ47WM