1st International Conference on Chemo and BioInformatics, ICCBIKG 2021, (347-350)
AUTHOR(S) / AUTOR(I): Emilija Milović, Nenad Janković, Jelena Petronijević, Nenad Joksimović
E-ADRESS / E-ADRESA: emilija.milovic@pmf.kg.ac.rs, nenad.jankovic@kg.ac.rs, jelena.petronijevic@pmf.kg.ac.rs, nenad.joksimovic@pmf.kg.ac.rs
DOI: 10.46793/ICCBI21.347M
ABSTRACT / SAŽETAK:
Tetrahydropyrimidines (THPMs) attracted attention as a very important class of aza heterocycles with broad pharmacological activities during the past years. In many studies have been proven that THPMs have anticancer, anti-inflammatory, antimicrobial, antioxidant, antifungal, anti-HIV activity.
Bearing in mind our interest in medicinal and Biginelli chemistry, we investigated interaction with important biomacromolecules (DNA, BSA) and our earlier synthetized THPMs derivatives with proven very good cytotoxic activity.[1]
Investigation of affinity of compounds A and B (Figure 1) to bind to bovine serum albumin (BSA) is based on the fact that the efficiency of drugs depends on their ability to bind for carrier protein. Binding properties were investigated by using the fluorescence emission titration of BSA with A and B. The obtained values of Ka, which are in optimum range which is considered to be 106-107M-1 indicate that both compounds have great ability to bind to BSA. In addition, Ka values for A-BSA and B-BSAshow that both compounds are suitable for drug-cell
KEY WORDS / KLJUČNE REČI:
tetrahydropyrimidines, BSA interaction
REFERENCES / LITERATURA:
- N.Janković et al., Discovery of the Biginelli hybrids as novel caspase-9 activators in apoptotic machines: Lipophilicity, molecular docking study, influence on angiogenesis gene and miR-21 expression levels, Bioorganic Chemistry 86 (2019) 569-582.
- S.M. Sondhi, R.N. Goyal, A.M. Lahoti, N. Singh, R. Shukla, R. Raghubir., Synthesis and biological evaluation of 2-thiopyrimidine derivatives, Bioorganic and Medicinal Chemistry 13 (2005) 3185-3195.
- A. Domling., The discovery of new isocyanide-based multi-component reactions, Current Opinion in Chemical Biology 4 (2000) 318-323.
- R.W. Armstrong, A.P. Combs, P.A. Tempest, S.D. Brown, T.A. Keating., Multiplecomponen condensation strategies for combinatorial library synthesis, Accounts of Chemical Research 29 (1996) 123-131.
- A. Mallick, S. C. Bera, S. Maiti, N. Chattopadhyay., Fluorometric investigation of interaction of 3- acetyl-4-oxo-6,7-dihydro-12H indolo-[2,3-a] quinolizine with bovine serum albumin, Biophysical Chemistry 112 (2004) 9-14.
- P. B. Kandagal, S. Ashoka, J. Seetharamappa, S. Shaikh, Y. Jadegoud, O. B. Ijare., Study of the interaction of an anticancer drug with human and bovine serum albumin: Spectroscopic approach, Journal of Pharmaceutical and Biomedical Analysis 41 (2006) 393-399.
- S. F. Sun, B. Zhou, H. N. Hou, Y. Liu, G. Y. Xiang., Studies on the interaction between Oxaprozin- E and bovine serum albumin by spectroscopic methods, International Journal of Biological Macromolecules 39 (2006) 197-200.
- D. C. Carter, J. X. Ho., Structure of Serum Albumin, Advances in Protein Chemistry 45 (1994) 153- 176.
- R. E. Olson, D. D. Christ., Plasma Protein Binding of Drugs, Annual Reports in Medicinal Chemistry 31 (1996) 327-336.
- C. Bertucci, E. Domenici., Reversible and Covalent Binding of Drugs to Human Serum Albumin: Methodological Approaches and Physiological Relevance, Current Medicinal Chemistry 9 (2002) 1463-1481.
- F. Kratz F, B. Elsadek., Clinical impact of serum proteins on drug delivery, Journal of Controlled Release 161 (2012) 429–445.
- W. L. Gabler., Fluxes and accumulation of tetracyclines by human blood cells, Research Communications in Chemical Pathology Pharmacology 72 (1991) 39-51.