Synthesis and Molecular Docking study of Beclomethasone Dipropionate Derivatives as Glucocorticoid Receptor Inhibitors

V. Venkata Narayana; S. Sethuvasan; Vinod H. Jadhav; D. Anantha Krishnan; M. Kesavan; K. Prema Latha; K.V.B. Ranjitha; B. Jagan Mohan Reddy

doi:10.14233/ajchem.2025.33345

Issue

Vol. 37 No. 4 (2025): Vol 37 Issue 4, 2025

Issue Published : 29 March 2025

This work is licensed under a Creative Commons Attribution 4.0 International License.

Synthesis and Molecular Docking study of Beclomethasone Dipropionate Derivatives as Glucocorticoid Receptor Inhibitors

https://doi.org/10.14233/ajchem.2025.33345

V. Venkata Narayana

Department of Chemistry, Adikavi Nannaya University, Rajamahendravaram-533296, India; Venkatasai Life Sciences Private Limited, Prashanth Nagar, Kukatpally, Hyderabad-500072, India

https://orcid.org/0009-0007-7617-1649

S. Sethuvasan

Venkatasai Life Sciences Private Limited, Prashanth Nagar, Kukatpally, Hyderabad-500072, India

https://orcid.org/0000-0002-2046-9362

Vinod H. Jadhav

Venkatasai Life Sciences Private Limited, Prashanth Nagar, Kukatpally, Hyderabad-500072, India

https://orcid.org/0009-0001-9378-6561

D. Anantha Krishnan

Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur-603203, India

https://orcid.org/0000-0003-2774-853X

M. Kesavan

Interdisciplinary Institute of Indian System of Medicine, SRM Institute of Science and Technology, Kattankulathur-603203, India

https://orcid.org/0000-0002-8669-0924

K. Prema Latha

Department of Chemistry, University College for Women, Koti, Osmania University, Hyderabad-500095, India

https://orcid.org/0000-0002-7542-2203

K.V.B. Ranjitha

Department of Chemistry, Adikavi Nannaya University, Rajamahendravaram-533296, India

https://orcid.org/0000-0001-8291-9245

B. Jagan Mohan Reddy

Department of Chemistry, Adikavi Nannaya University, Rajamahendravaram-533296, India

https://orcid.org/0000-0001-9357-9610

Corresponding Author(s) : B. Jagan Mohan Reddy

drbjaganreddy@gmail.com

Asian Journal of Chemistry, Vol. 37 No. 4 (2025): Vol 37 Issue 4, 2025
Article Published : 29 March 2025

Abstract

The present study involved the synthesis of four beclomethasone dipropionate (BDP) derivatives with structural modifications at the C9, C11 and C21 carbon atoms and changing the substituents with halogen (Cl & Br) and alkyl moieties. The synthesis was achieved through a series of stepwise reactions and the derivatives were characterized by mass & ¹H NMR spectral data and by HPLC analysis. In silico molecular docking studies demonstrated that all the synthesized BDP derivatives (5, 7, 9 and 12) exhibited favourable binding interactions with the glucocorticoid receptor (GR). The docking results revealed that all the BDP derivatives were in good agreement, particularly compound 5, which had strong binding affinity with the GR protein, comparable to the co-crystal. Based on the results, it was found that all BDP derivatives and its acts as drug-like molecules.

Keywords

Beclomethasone dipropionate Molecular docking Glucocorticoid receptor

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Narayana, V. V.; Sethuvasan, S.; Jadhav, V. H.; Krishnan, D. A.; Kesavan, M.; Latha, K. P.; Ranjitha, K.; Reddy, B. J. M. Synthesis and Molecular Docking Study of Beclomethasone Dipropionate Derivatives As Glucocorticoid Receptor Inhibitors. ajc 2025, 37, 804-810.

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References

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M. De Bock and P. Sienaert, World J. Biol. Psych., 25, 161 (2024); https://doi.org/10.1080/15622975.2024.2312572

B. Brazzini and N. Pimpinelli, Am. J. Clin. Dermatol., 3, 47 (2002); https://doi.org/10.2165/00128071-200203010-00005

D.H. Kim, H.J. Lee, C.W. Park, K.H. Kim, K.H. Lee, B.I. Ro and S.H. Cho, Ann. Dermatol., 25, 17 (2013); https://doi.org/10.5021/ad.2013.25.1.17

J.S. Vilsvik, A.O. Jenssen and R. Walstad, Clin. Exp. Allergy, 5, 291 (1975); https://doi.org/10.1111/j.1365-2222.1975.tb01865.x

E. Nucera, A. Buonomo, E. Pollastrini, T. De Pasquale, M. Del Ninno, C. Roncallo, D. Schiavino and G. Patriarca, Dermatology, 204, 248 (2002); https://doi.org/10.1159/000057891

G.D. Raphael, R.Q. Lanier, J. Baker, L. Edwards, K. Rickard and W.R. Lincourt, J. Allergy Clin. Immunol., 103, 796 (1999); https://doi.org/10.1016/S0091-6749(99)70422-7

A. Miller-Larsson, P. Jansson, A. Runström and R. Brattsand, Am. J. Respir. Crit. Care Med., 162, 1455 (2000); https://doi.org/10.1164/ajrccm.162.4.9806112

K. Nishimura, H. Koyama, A. Ikeda, M. Tsukino, T. Hajiro, M. Mishima and T. Izumi, Chest, 115, 31 (1999); https://doi.org/10.1378/chest.115.1.31

G. Nicolini, N. Scichilone, A. Bizzi, A. Papi and L.M. Fabbri, Ther. Clin. Risk Manag., 4, 855 (2008); https://doi.org/10.2147/TCRM.S3126

A. Ahmet, H. Kim and S. Spier, Allergy Asthma Clin. Immunol., 7, 13 (2011); https://doi.org/10.1186/1710-1492-7-13

A. Renner, K. Marth, R. Breyer-Kohansal and W. Pohl, Respir. Med., 207, 107097 (2023); https://doi.org/10.1016/j.rmed.2022.107097

Y. He, W. Yi, K. Suino-Powell, X.E. Zhou, W.D. Tolbert, X. Tang, J. Yang, H. Yang, J. Shi, L. Hou, H. Jiang, K. Melcher and H.E. Xu, Cell Res., 24, 713 (2014); https://doi.org/10.1038/cr.2014.52

F. Spada, T.M. Barnes and K.A. Greive, Australas. J. Dermatol., 59, e168 (2018); https://doi.org/10.1111/ajd.12762

G. Caramori, S. Mumby, G. Girbino, K.F. Chung and I.M. Adcock, in eds.: M.J. Parnham, F.P. Nijkamp and A.G. Rossi, Nijkamp and Parnham’s Principles of Immunopharmacology, Springer International Publishing, Cham, pp. 661-688 (2019).

D.T. Welideniya, A.S. Jayathilaka, A.D. Acharige, K.A.U. Samanthi, U.K. Wanninayake, W. Rajapaksha, C.C. Fernando, M. Hewadikaram, S.S. Perera, J. Buddhika, P. Gunasekara, V. Karunaratne, G.A.J. Amaratunga and D.S. Gunasekera, Steroids, 177, 108948 (2022); https://doi.org/10.1016/j.steroids.2021.108948

H. Wang, Z. Niu, Q. Wang, H. Li and J. Su, China Patent CN111944002 (2020).

R.K. Bledsoe, V.G. Montana, T.B. Stanley, C.J. Delves, C.J. Apolito, D.D. McKee, T.G. Consler, D.J. Parks, E.L. Stewart, T.M. Willson, M.H. Lambert, J.T. Moore, K.H. Pearce and H.E. Xu, Cell, 110, 93 (2002); https://doi.org/10.1016/S0092-8674(02)00817-6

L.L.C. Schrödinger, Schrodinger release 2014-2; New York, NY: Schrödinger, LLC (2014).

T. Halgren, Chem. Biol. Drug Des., 69, 146 (2007); https://doi.org/10.1111/j.1747-0285.2007.00483.x

R.A. Friesner, J.L. Banks, R.B. Murphy, T.A. Halgren, J.J. Klicic, D.T. Mainz, M.P. Repasky, E.H. Knoll, M. Shelley, J.K. Perry, D.E. Shaw, P. Francis and P.S. Shenkin, J. Med. Chem., 47, 1739 (2004); https://doi.org/10.1021/jm0306430

H. Wang, R. Aslanian and V.S. Madison, J. Mol. Graph. Model., 27, 512 (2008); https://doi.org/10.1016/j.jmgm.2008.09.002

J.E. Huber and J.A. Fleming, 9a-Dehalogenation Process, US Patent, US5426198 (1995).

M.J. Green, H.J. Shue, E.L. Shapiro and M.A. Gentles, German patent CH637406 (1983).

Author biographies is not available.