Disclosure the Relationship ”Structure Biology Activity” on the Basis of Conformational Analysis of the Brassinosteroid’s Stereoisomers by the Molecular Modeling Methods

V. M. Andrianov ; I. V. Anishchenko

Matematičeskaâ biologiâ i bioinformatika, Tome 9 (2014) no. 2, pp. 386-395.

Résumé

The conformational analysis of one of the most biologically active brassinosteroids, natural brassinolide, as well as of the less active natural 24-epibrassinolide, synthetics (22S,23S)-24-epibrassinolide and (22S,23S)-homobrassinolide was carried out by molecular mechanics and the DFT quantum chemical calculations followed by the comparison of their side chain structures. The 22R,23R,24S configuration of two hydroxyls and the methyl group of the brassinolide side chain was shown to support the structures in which its diol system makes the intramolecular O6…H(O5) hydrogen bond. At the same time, the O6H hydroxyl group is unbounded and may participate in forming the intermolecular hydrogen bond with a receptor. As opposed to this observation, the 22S,23S,24R-configuration of (22S,23S)-24-epibrassinolide is in line with the structures where the O6H hydroxyl group is screened by the 21-methyl group, causing the less biological activity of this hormone. It was shown that important factor of high brassinosteroid’s bioactivity is the curvature of their side chain in the line of the $\beta$-side of the steroid’s backbone, as well.

Bibliographie

[1] Misharin A. Yu., Mehtiev A. R., Zhabinskii V. N., Khripach V. A., Timofeev V. P., Tkachev Y. V., “Toxicity of (22R,23R)-22,23-dihydroxystigmastane derivatives to cultured cancer cells”, Steroids, 75:3 (2010), 287–294 | DOI

[2] Zullo M. A. T., Adam G., “Brassinosteroid phytohormones: structure, bioactivity and applications”, Brazilian J. Plant Physiology, 14:3 (2002), 143–181 | DOI

[3] Brosa C., Capdevila J. M., Zamora I., “Brassinosteroids: a new way to define the structural requirements”, Tetrahedron, 52:7 (1996), 2435–2448 | DOI

[4] Alvarez-Ginarte Y. M., Crespo-Otero R., Marrero-Ponce Y., Montero L. A., Ruiz-Garcia J. A., Padron-Garcia A., Zaragoza F. T., “Quantitative Structure-Activity Relationship of the $4$, $5\alpha$ Dihydrotestosterone Steroid Family”, QSAR Comb. Sci., 25:10 (2006), 881–894 | DOI

[5] Morera-Boado C., Alonso-Becerra E., Montero-Cabrera L. A., Gonzalez-Jonte R., “Validation of performances of some semiempirical Hamiltonians for predicting molecular structure calculation of natural brassinosteroids: Towards understanding their biological activity by electron exchange effects”, J. Mol. Struct.: THEOCHEM, 819:1–3 (2007), 109–120 | DOI

[6] Andrianov V. M., “Teoreticheskie issledovaniya molekulyarnoi struktury ryada sinteticheskikh i prirodnykh brassinosteroidov v svyazi s ikh biologicheskoi aktivnostyu”, Zhurn. strukt. khimii, 52:4 (2011), 792–797

[7] Uesusuki S., Watanabe B., Yamamoto S., Otsuki J., Nakagawa Y., Miyagawa H., “Synthesis of brassinosteroids of varying acyl side chains and evaluation of their brassinolide-like activity”, Biosci. Biotechnol. Biochem., 68:5 (2004), 1097–1105 | DOI

[8] Drosihn S., Porzel A., Brandt W., “Determination of preferred conformations of brassinosteroids by means of NMR investigations and Boltzmann statistical analysis of simulated annealing calculations”, J. Mol. Model., 7:4 (2001), 34–42 | DOI

[9] Stoldt M., Porzel A., Adam G., Brandt W., “Side Chain Conformation of the Growth-Promoting Phytohormones Brassinolide and 24-Epibrassinolide”, Magn. Res. Chem., 35:9 (1997), 629–636 | 3.0.CO;2-E class='badge bg-secondary rounded-pill ref-badge extid-badge'>DOI

[10] Wiberg K. B., Boyd R. H., “Application of strain energy minimization to the dynamics of conformational changes”, J. Am. Chem. Soc., 94:24 (1972), 8426–8430 | DOI

[11] Voigt B., Porzel A., Wagner C., Merzweiler K., Private Communication to the Cambridge Structural Database, deposition number CCDC 116995, 2001

[12] Voigt B., Porzel A., Wagner C., Merzweiler K., Private Communication to the Cambridge Structural Database, deposition number CCDC 119112, 2001

[13] Kutschabsky L., Reck G., Private Communication to the Cambridge Structural Database, deposition number CCDC 201799, 2003

[14] Kutschabsky L., Adam G., Vorbrodt H.-M., “Molekül- und Kristallstruktur von (22S,23S)-Homobrassinolid”, Z. Chem., 30 (1990), 136–137 | DOI

[15] Stephens P. J., Devlin F. J., Chabalowski C. F., Frisch M. J., “Ab Initio Calculation of Vibrational Absorption and Circular Dichroism Spectra Using Density Functional Force Fields”, J. Phys. Chem., 98:45 (1994), 11623–11627 | DOI

[16] Frisch M. J., Trucks G. W., Schlegel H. B., Scuseria G. E., Robb M. A., Cheeseman J. R., Scalmani G., Barone V., Mennucci B., Petersson G. A., Nakatsuji H., Caricato M., Li X., Hratchian H. P., Izmaylov A. F., Bloino J., Zheng G., Sonnenberg J. L., Hada M., Ehara M., Toyota K., Fukuda R., Hasegawa J., Ishida M., Nakajima T., Honda Y., Kitao O., Nakai H., Vreven T., Montgomery J. A. (Jr.), Peralta J. E., Ogliaro F., Bearpark M., Heyd J. J., Brothers E., Kudin K. N., Staroverov V. N., Keith T., Kobayashi R., Normand J., Raghavachari K., Rendell A., Burant J. C., Iyengar S. S., Tomasi J., Cossi M., Rega N., Millam J. M., Klene M., Knox J. E., Cross J. B., Bakken V., Adamo C., Jaramillo J., Gomperts R., Stratmann R. E., Yazyev O., Austin A. J., Cammi R., Pomelli C., Ochterski J. W., Martin R. L., Morokum K., Zakrzewski V. G., Voth G. A., Salvador P., Dannenberg J. J., Dapprich S., Daniels A. D., Farkas O., Foresman J. B., Ortiz J. V., Cioslowski J., Fox D. J., Gaussian 09, Revision B.01, Gaussian, Inc., Wallingford CT, 2010

[17] Bajguz A., Czerpak R., “Physiological and biochemical role of Brassinosteroids and their structure-activity relationship in the Green Alga Chlorella vulgaris Beijerinck (Chlorophyceae)”, J. Plant Growth Regul., 17 (1998), 131–139 | DOI

[18] Takatsuto S., Yazawa N., Ikekawa N.,. Morishita T., Abe H., “Synthesis of (24R)-2tbHomobrassinolide analogues and structure-activity relationships of brassinosteroids in the rice-lamina inclination test”, Phytochemistry, 22:6 (1983), 1393–1397 | DOI

[19] Takatsuto S., Yazawa N., Ikekawa N., Takema T., Takeuchi Y., Koguchi M., “Structure-activity relationship of brassinosteroids”, Phytochemistry, 22:11 (1983), 2437–2441 | DOI

[20] Thompson M. J., Meudt W. J., Mandava N. B., Dutky S. R., Lusby W. R., Spaulding D. W., “Synthesis of brassinosteroids and relationship of structure to plant growth-promoting effects”, Steroids, 39:1 (1982), 89–105 | DOI

[21] Khripach V. A., Zhabinskii V. N., Ivanova G. V., Fando G. P., Tsavlovskii D. V., Khripach N. B., Lyakhov A. S., Misharin A. Yu., “NMR and X-ray studies of isomeric 22,23-dihydroxy stigmastanes”, J. Mol. Struct., 975:1–3 (2010), 242–246 | DOI

[22] She J., Han Zh., Kim T.-W., Wang J., Cheng W., Chang J., Shi S., Wang J., Yang M., Wang Z.-Y., Chai J., “Structural insight into brassinosteroid perception by BRI1”, Nature, 474 (2011), 472–476 | DOI