Computational discovery of uterotonic agents: Molecular docking and dynamic simulations of Caesalpinia bonduc phytoconstituents

Jinal Tandel; Usmangani Chhalotiya; Heta Kachhiya; Ashish Patel; Parth Thakor; Jignesh Prajapati; Dweipayan Goswami

doi:10.12991/jrespharm.1798416

Computational discovery of uterotonic agents: Molecular docking and dynamic simulations of Caesalpinia bonduc phytoconstituents

Abstract

Molecular modeling is widely applied to study the interaction and binding affinity of biological activity of protein and peptide. Molecular dynamics simulation can provide valuable information in deciphering functional mechanisms of protein and other biomolecules, Caesalpinia bonduc (L) Roxb contains compounds that bind with estrogen receptors, PGs receptors, Oxytocin receptors, Alpha-adrenergic receptors, etc. which are found on the surface of myometrial cells that affect contractility. The present study focuses on understanding the molecular mechanism of bioactive compounds of Caesalpinia bonduc (L) Roxb for uterine contraction. The molecular docking of compounds that are present in Caesalpinia bonduc (L) Roxb named α caesalpin, β caesalpin, ε caesalpin, caesalpin F, and Bonducellin were performed against 1FDS, 3S79, 1E3G, 3ERT targets. Molecular docking and dynamic simulation studies were established by applying Glide precision mode and Maestro respectively. The Molecular dynamic (MD) simulation was performed to analyse the stability and interactions of the bioactive compounds from Caesalpinia bonduc (L) Roxb leaf extract. Docking analysis for active biomarkers of Caesalpinia bonduc (L) Roxb with target proteins revealed compound binding towards selected proteins and activity against uterus contraction. Bonducellin exhibits the highest binding scores among all compounds, the remaining α caesalpin, ε caesalpin, β caesalpin, and caesalpin F, were also found to have prominent binding towards selected proteins. This stabilization is achieved through strong and stable interactions, as evidenced by the MD simulation data. Among the compounds. The results suggest that Bonducellin and related compounds hold promise as multi-target Uterotonic agents, with potential applications in managing labour and reducing postpartum haemorrhage..

Keywords

References

Pagadala NS, Syed K, Tuszynski J. Software for molecular docking: a review. Biophys Rev. 2017;9:91– 102. https://doi.org/10.1007/s12551-016-0247-1
Vidal-Limon A, Aguilar-Toalá JE, Liceaga AM. Integration of Molecular Docking Analysis and Molecular Dynamics Simulations for Studying Food Proteins and Bioactive Peptides. J Agric Food Chem. 2022;70:934–943. https://doi.org/10.1021/acs.jafc.1c06110
Prevention of Postpartum Hemorrhage Initiative. Fact sheets: Uterotonic drugs for the prevention and treatment of postpartum hemorrhage. 2008. https://www.path.org/our- impact/resources/prevention-of-postpartum-hemorrhage-fact-sheets/
Ruysen H, Shabani J, Hanson C, Day LT, Pembe AB, Peven K, Rahman QS, Thakur N, Shirima K, Tahsina T, Gurung R, Tarimo MN, Moran AC, Lawn JE; EN-BIRTH Study Group. Uterotonics for prevention of postpartum haemorrhage: EN-BIRTH multi-country validation study. BMC Pregnancy Childbirth. 2021;21(Suppl 1):230. https://doi.org/10.1186/s12884-020-03420-x
WHO. Caesarean section rates continue to rise, amid growing inequalities in access. 2021. https://www.who.int/news/item/16-06-2021-caesarean-section-rates-continue-to-rise-amid- growing-inequalities-in-access.
Neu J, Rushing J. Cesarean Versus Vaginal Delivery: Long-term Infant Outcomes and the Hygiene Hypothesis. Clin Perinatol. 2011;38:321–331. https://doi.org/10.1016/j.clp.2011.03.008
Chen H, Tan D. Cesarean Section or Natural Childbirth? Cesarean Birth May Damage Your Health. Front Psychol. 2019;10:351. https://doi.org/10.3389/fpsyg.2019.00351
Dyer RA, van Dyk D, Dresner A. The use of uterotonic drugs during caesarean section. Int J Obstet Anesth. 2010;19:313–319. https://doi.org/10.1016/j.ijoa.2010.04.011

Roqaiya M, Majeedi SF, Saiyed A, Begum W. A Review on Herbs with Uterotonic Property. J Phytopharmacol. 2015;4:190–196.
Raghav PK, Singh V. Review on pharmacological properties of Caesalpinia bonduc L. Int J Med Arom Plants. 2012;2:514–30.
Gruber C, O’Brien M. Uterotonic plants and their bioactive constituents. Planta Med. 2011;77:207–220. https://doi.org/10.1055/s-0030-1250317
Mehra B, Kumar Maurya S, Dwivedi KD. Pharmacognostic evaluation of Latakaranja (Caesalpinia bonduc [L.] Roxb.). Int J Green Pharm. 2015;9:63–74.
Handa SS, Singh GN, Kapoor YK. Quality standards of Indian Medicinal Plants. vol. 2. First ed., Indian Council of Medical Research, New Delhi, 2005.
Dhankhar N, Khan N, Kumar S, Singh RP. A pharmacognostic and pharmacological overview on Caesalpinia bonducella. Res J Pharm Biol Chem Sci. 2012;3:480–496.
Kandasamy V, Balasundaram U. Caesalpinia bonduc (L.) Roxb. as a promising source of pharmacological compounds to treat Poly Cystic Ovary Syndrome (PCOS): A review. J Ethnopharmacol. 2021;279:114375. https://doi.org/10.1016/j.jep.2021.114375
Sasidharan S, Kumar Kp S, Das K, Nair H. Caesalpinia bonduc: A Ubiquitous yet Remarkable Tropical Plant Owing Various Promising Pharmacological and Medicinal Properties with Special References to the Seed. Med Aromat Plants. 2021;10:394–412.
Deepak Pandey D, Kumar A, Pal Jain A. Caesalpinia bonducella: A pharmacological important plant. Pharm Innov J. 2018;7:190–193.
Akbar S. Caesalpinia bonduc (L.) Roxb. (Fabaceae/Caesalpiniaceae), Handbook of 200 Medicinal Plants, Cham: Springer International Publishing, 2020 https://doi.org/10.1007/978-3-030-16807-0_51
Manikandaselvi S, Vadivel V, Brindha P. Caesalpinia bonducella L.: A nutraceutical plant. J Chem Pharm Res. 2015;7:137–142.
Muruganantham N, Basavaraj KH, Dhanabal SP, Praveen TK, Shamasundar NM, Rao KS. Screening of Caesalpinia bonduc leaves for antipsoriatic activity. J Ethnopharmacol. 2011;133:897–901. https://doi.org/10.1016/j.jep.2010.09.026
Tandel JN, Chhalotiya U, Kachhiya H, Tandel D. Advanced thin-layer chromatography‒mass spectrometry validation and comprehensive analysis of bioactive phytochemicals in Caesalpinia bonduc leaf extract. JPC – Journal of Planar Chromatography – Modern TLC. 2025; 38:83–93. https://doi.org/10.1007/s00764-025-00336-0.
Datté JY, Traoré A, M. Offoumou A, Ziegler A. Effects of leaf extract of Caesalpinia bonduc (Caesalpiniaceae) on the contractile activity of uterine smooth muscle of pregnant rats. J Ethnopharmacol. 1998;60:149–155. https://doi.org/10.1016/S0378-8741(97)00144-X
Datté JY, Yapo PA, Kouamé-Koffi GG, Kati-Coulibaly S, Amoikon KE, Offoumou AM. Leaf extract of Caesalpinia bonduc Roxb. (Caesalpiniaceae) induces an increase of contractile force in rat skeletal muscle in situ. Phytomedicine 2004;11:235–241. https://doi.org/10.1078/0944-7113-00292
Bleyere MN, Konan A, Amonkan A, Bouafou MK. Why african traditional birth attendants used Ceasalpinia bonduc leaves to facilitate childbirth in parturient women? Int J Pharm Rev Res. 2014;4:11– 16.
Rosaeg OP, Cicutti NJ, Labow RS. The effect of oxytocin on the contractile force of human atrial trabeculae. Anesth Analg. 1998;86:40–44. https://doi.org/10.1097/00000539-199801000-00008
Arias F. Pharmacology of oxytocin and prostaglandins. Clin Obstet Gynecol. 2000;43:455–468. https://doi.org/10.1097/00003081-200009000-00006
Bergum D, Lonnée H, Hakli TF. Oxytocin infusion: acute hyponatraemia, seizures and coma. Acta Anaesthesiol Scand. 2009;53:826–827. https://doi.org/10.1111/j.1399-6576.2009.01964.x
Ojha D, Raval P, Pujeri S, Shirguppi S. Evaluation of the efficacy of Latakaranja as antispasmodic drug in Kastaartava - A randomised clinical control trial. J Ayurveda Integr Med Sci 2020;5:116-122. http://dx.doi.org/10.21760/jaims.5.5.15.
McEvoy A, Sabir S. Physiology, Pregnancy Contractions, StatPearls, 2024.
Pires DE V., Blundell TL, Ascher DB. pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. J Med Chem. 2015;58:4066–4072. https://doi.org/10.1021/acs.jmedchem.5b00104.
Bowers KJ, Sacerdoti FD, Salmon JK, Shan Y, Shaw DE, Chow E. Molecular dynamics---Scalable algorithms for molecular dynamics simulations on commodity clusters. Proceedings of the 2006 ACM/IEEE conference on Supercomputing - SC ’06, New York, New York, USA: ACM Press; 2006, p. 84. https://doi.org/10.1145/1188455.1188544.

Details

Primary Language

English

Subjects

Pharmaceutical Chemistry, Pharmaceutical Microbiology

Journal Section

Research Article

Authors

Jinal Tandel
0000-0003-1669-6519
India

Usmangani Chhalotiya ^*
0000-0003-1183-2761
India

Heta Kachhiya
0000-0003-4534-6243
India

Ashish Patel
0000-0001-5773-3756
India

Parth Thakor This is me
0000-0002-7477-0177
India

Jignesh Prajapati This is me
0000-0001-8700-9929
India

Dweipayan Goswami This is me
0000-0003-0165-0294
India

Publication Date

November 2, 2025

Submission Date

December 2, 2024

Acceptance Date

January 11, 2025

Published in Issue

Year 2025 Volume: 29 Number: 6

DOI

https://doi.org/10.12991/jrespharm.1798416

IZ

https://izlik.org/JA25PD59PJ

Cite

RIS / Bibtex

APA

Tandel, J., Chhalotiya, U., Kachhiya, H., Patel, A., Thakor, P., Prajapati, J., & Goswami, D. (2025). Computational discovery of uterotonic agents: Molecular docking and dynamic simulations of Caesalpinia bonduc phytoconstituents. Journal of Research in Pharmacy, 29(6), 2610-2624. https://doi.org/10.12991/jrespharm.1798416

AMA

1.Tandel J, Chhalotiya U, Kachhiya H, et al. Computational discovery of uterotonic agents: Molecular docking and dynamic simulations of Caesalpinia bonduc phytoconstituents. J. Res. Pharm. 2025;29(6):2610-2624. doi:10.12991/jrespharm.1798416

Chicago

Tandel, Jinal, Usmangani Chhalotiya, Heta Kachhiya, et al. 2025. “Computational Discovery of Uterotonic Agents: Molecular Docking and Dynamic Simulations of Caesalpinia Bonduc Phytoconstituents”. Journal of Research in Pharmacy 29 (6): 2610-24. https://doi.org/10.12991/jrespharm.1798416.

EndNote

Tandel J, Chhalotiya U, Kachhiya H, Patel A, Thakor P, Prajapati J, Goswami D (November 1, 2025) Computational discovery of uterotonic agents: Molecular docking and dynamic simulations of Caesalpinia bonduc phytoconstituents. Journal of Research in Pharmacy 29 6 2610–2624.

IEEE

[1]J. Tandel et al., “Computational discovery of uterotonic agents: Molecular docking and dynamic simulations of Caesalpinia bonduc phytoconstituents”, J. Res. Pharm., vol. 29, no. 6, pp. 2610–2624, Nov. 2025, doi: 10.12991/jrespharm.1798416.

ISNAD

Tandel, Jinal - Chhalotiya, Usmangani - Kachhiya, Heta - Patel, Ashish - Thakor, Parth - Prajapati, Jignesh - Goswami, Dweipayan. “Computational Discovery of Uterotonic Agents: Molecular Docking and Dynamic Simulations of Caesalpinia Bonduc Phytoconstituents”. Journal of Research in Pharmacy 29/6 (November 1, 2025): 2610-2624. https://doi.org/10.12991/jrespharm.1798416.

JAMA

1.Tandel J, Chhalotiya U, Kachhiya H, Patel A, Thakor P, Prajapati J, Goswami D. Computational discovery of uterotonic agents: Molecular docking and dynamic simulations of Caesalpinia bonduc phytoconstituents. J. Res. Pharm. 2025;29:2610–2624.

MLA

Tandel, Jinal, et al. “Computational Discovery of Uterotonic Agents: Molecular Docking and Dynamic Simulations of Caesalpinia Bonduc Phytoconstituents”. Journal of Research in Pharmacy, vol. 29, no. 6, Nov. 2025, pp. 2610-24, doi:10.12991/jrespharm.1798416.

Vancouver

1.Jinal Tandel, Usmangani Chhalotiya, Heta Kachhiya, Ashish Patel, Parth Thakor, Jignesh Prajapati, Dweipayan Goswami. Computational discovery of uterotonic agents: Molecular docking and dynamic simulations of Caesalpinia bonduc phytoconstituents. J. Res. Pharm. 2025 Nov. 1;29(6):2610-24. doi:10.12991/jrespharm.1798416