3rd International Conference on Chemo and BioInformatics, Kragujevac, September 25-26. 2025. (pp. 440-443)
АУТОР(И) / AUTHOR(S): Vladimir Simić, Žiko Milanović, Emina Mrkalić, Miljan Milošević, Marko Antonijević, Goran Kaluđerović
Download Full Pdf 
DOI: 10.46793/ICCBIKG25.440S
САЖЕТАК / ABSTRACT:
Renin is a key regulator in the renin-angiotensin-aldosterone system (RAAS) and an established therapeutic target for hypertension. Although direct renin inhibitors such as Aliskiren are clinically used, new candidates with improved efficacy are still required. This work investigates the transport dynamics of organotin(IV) compounds (Ph₃SnL1–Ph₃SnL5) within a three-dimensional finite element liver model incorporating an embedded vascular network. Diffusion coefficients, estimated via the Stokes–Einstein relation, ranged from 4.31 × 10⁻4 mm² s⁻1 (Ph₃SnL1) to 3.80 × 10⁻4 mm² s⁻1 (Ph₃SnL5), compared to 3.78 × 10⁻4 mm² s⁻1 for Aliskiren. Simulations showed rapid compound penetration from capillaries to tissue, with diffusion kinetics strongly dependent on individual coefficients. Among all, Ph₃SnL1 exhibited the fastest and most homogeneous distribution, while Aliskiren displayed slower transport. These findings highlight the capability of advanced computational modeling to evaluate candidate renin inhibitors and suggest organotin(IV) compounds as promising leads for antihypertensive drug development.
КЉУЧНЕ РЕЧИ / KEYWORDS:
renin, hypertension, finite element method, organotin(IV) complexes, liver model
ПРОЈЕКАТ / ACKNOWLEDGEMENT:
The authors wish to acknowledge the Ministry of Science, Technological Development and Innovation of the Republic of Serbia (Agreements No. 451-03-136/2025-03/200378).
ЛИТЕРАТУРА / REFERENCES:
- Fountain JH, Kaur J, Lappin SL. Physiology, Renin Angiotensin System. 2023 Mar 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; Jan–. PMID: 29261862.
- L. Zagorchev, P. Oses, Z.W. Zhuang, K. Moodie, M.J. Mulligan-Kehoe, M. Simons, T. Couffinhal (2010), Micro computed tomography for vascular exploration, J Angiogenes Res, 7.
- Kojic, M., Milosevic, M., Ziemys, A. (2022). Computational Models in Biomedical Engineering: Finite Element Models Based on Smeared Physical Fields: Theory, Solutions, and Software. Academic Press.
- Kojic, M., Milosevic, M., Simic, V., Koay, E. J., Kojic, N., Ziemys, A., Ferrari, M. (2017). Extension of the composite smeared finite element (CSFE) to include lymphatic system in modeling mass transport in capillary systems and biological tissue. Journal of the Serbian Society for Computational Mechanics, 11(2), 108.
- Kojic, M. (2018). Smeared concept as a general methodology in finite element modeling of physical fields and mechanical problems in composite media. J. Serb. Soc. Comput. Mech, 12, 1-16.
- Kojic, M., Milosevic, M., Simic, V., Koay, E. J., Fleming, J. B., Nizzero, S., Ferrari, M. (2017). A composite smeared finite element for mass transport in capillary systems and biological tissue. Computer methods in applied mechanics and engineering, 324, 413-437.
- Kojić, M., Slavković, R., Živković, M., Grujović, N., Filipović, N. (1998/2010) PAK – FE Software for structural analysis, field problems, multiphysics and biomechanics. Kragujevac: Faculty of Mechanical Engineering.
- Milanović Ž., Mrkalić E., Antonijević M., Rüffer T., Simić V., Milošević M., Kaluđerović G., Exploring (alkyl-ω-ol)triphenyltin(IV) compounds as renin inhibitors: Structural insights, binding dynamics, and pharmacokinetic profiling for antihypertensive therapy, Inorganic Chemistry Communications, 2025, ISSN 1387-7003, https://doi.org/10.1016/j.inoche.2025.115329.