Synthesis, structural characterization, DFT calculations and antiproliferative evaluation of novel spirohydantoin derivatives containing a substituted benzyl moiety
Autori
Lazić, Anita M.Radovanović, Lidija D.
Božić, Bojan Đ.
Božić Nedeljković, Biljana Đ.
Vitnik, Vesna D.
Vitnik, Željko J.
Rogan, Jelena R.
Valentić, Nataša V.
Ušćumlić, Gordana S.
Trišović, Nemanja P.
Članak u časopisu (Recenzirana verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Two series of cycloalkanespiro-5-hydantoins, namely cyclohexanespiro-5-hydantoins and cycloheptanespiro-5-hydantoins with a 4-substituted benzyl or a 2-(4-substituted phenyl)-2-oxoethyl group at N3 position, were synthesized and their effects on proliferation of human colon (HCT-116), leukemia (K562) and breast (MDA-MB-231) cancer cell lines were tested. For comparison, we also described the 5,5-diphenylhydantoin analogues. The structural features of the investigated compounds were characterized by elemental analysis, FT-IR, UV–Vis, 1 H and 13 C NMR spectroscopy and X-ray crystallography. Regarding their structure–activity relationships, it was shown that the substitution on the benzyl moiety with the methoxy, chloro or bromo group potentiated the antiproliferative activity relative to the parent compounds, while an increase in the size of the cycloalkyl group resulted mostly in a decrease of the antiproliferative activity. The single crystal X-ray analysis revealed the existence of di...mers and chains formed by the N–H⋯O hydrogen bonds. The analysis of the molecular descriptors of Lipinski demonstrated that all investigated compounds obeyed the rule of five. To further understand their geometry and electronic structure, DFT calculations with B3LYP method using 6-311++G(d,p) basic set were performed. In this context, the UV–Vis spectra of the investigated compounds were analyzed in detail, whereby the predicted absorption spectra from DFT calculation matched the experimentally obtained ones, with a good correlation. The interesting physico-chemical and pharmacologically relevant properties of the investigated compounds warrant their further investigation.
Ključne reči:
Antiproliferative activity / DFT calculation / Spirohydantoin / X-ray structure determinationIzvor:
Journal of Molecular Structure, 2019, 1180, 48-62Izdavač:
- Elsevier B.V.
Finansiranje / projekti:
- Proučavanje sinteze, strukture i aktivnosti organskih jedinjenja prirodnog i sintetskog porekla (RS-MESTD-Basic Research (BR or ON)-172013)
- Racionalni dizajn i sinteza biološki aktivnih i koordinacionih jedinjenja i funkcionalnih materijala, relevantnih u (bio)nanotehnologiji (RS-MESTD-Basic Research (BR or ON)-172035)
- Bioinformatički metodi za detekciju promotera i teorijsko modelovanje genskih kola (RS-MESTD-Basic Research (BR or ON)-173052)
- Struktura genetičke varijabilnosti mikrosatelitskih markera u stanovništvu Srbije i Crne Gore (RS-MESTD-MPN2006-2010-145007)
Napomena:
- Published version: http://technorep.tmf.bg.ac.rs/handle/123456789/4324
- This is the peer-reviewed version of the following article: Lazić A, Radovanović L, Božić B, Božić-Nedeljković B, Vitnik V, Vitnik Ž, Rogan J, Valentić N, Ušćumlić G, Trišović N. Synthesis, structural characterization, DFT calculations and antiproliferative evaluation of novel spirohydantoin derivatives containing a substituted benzyl moiety. in Journal of Molecular Structure. 2019;1180:48-62. https://doi.org/10.1016/j.molstruc.2018.11.071
Povezane informacije:
- Verzija dokumenta
http://technorep.tmf.bg.ac.rs/handle/123456789/4324 - Verzija dokumenta
https://doi.org/10.1016/j.molstruc.2018.11.071
DOI: 10.1016/j.molstruc.2018.11.071
ISSN: 0022-2860
WoS: 000457660300007
Scopus: 2-s2.0-85059311562
Kolekcije
Institucija/grupa
Inovacioni centarTY - JOUR AU - Lazić, Anita M. AU - Radovanović, Lidija D. AU - Božić, Bojan Đ. AU - Božić Nedeljković, Biljana Đ. AU - Vitnik, Vesna D. AU - Vitnik, Željko J. AU - Rogan, Jelena R. AU - Valentić, Nataša V. AU - Ušćumlić, Gordana S. AU - Trišović, Nemanja P. PY - 2019 UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/5038 AB - Two series of cycloalkanespiro-5-hydantoins, namely cyclohexanespiro-5-hydantoins and cycloheptanespiro-5-hydantoins with a 4-substituted benzyl or a 2-(4-substituted phenyl)-2-oxoethyl group at N3 position, were synthesized and their effects on proliferation of human colon (HCT-116), leukemia (K562) and breast (MDA-MB-231) cancer cell lines were tested. For comparison, we also described the 5,5-diphenylhydantoin analogues. The structural features of the investigated compounds were characterized by elemental analysis, FT-IR, UV–Vis, 1 H and 13 C NMR spectroscopy and X-ray crystallography. Regarding their structure–activity relationships, it was shown that the substitution on the benzyl moiety with the methoxy, chloro or bromo group potentiated the antiproliferative activity relative to the parent compounds, while an increase in the size of the cycloalkyl group resulted mostly in a decrease of the antiproliferative activity. The single crystal X-ray analysis revealed the existence of dimers and chains formed by the N–H⋯O hydrogen bonds. The analysis of the molecular descriptors of Lipinski demonstrated that all investigated compounds obeyed the rule of five. To further understand their geometry and electronic structure, DFT calculations with B3LYP method using 6-311++G(d,p) basic set were performed. In this context, the UV–Vis spectra of the investigated compounds were analyzed in detail, whereby the predicted absorption spectra from DFT calculation matched the experimentally obtained ones, with a good correlation. The interesting physico-chemical and pharmacologically relevant properties of the investigated compounds warrant their further investigation. PB - Elsevier B.V. T2 - Journal of Molecular Structure T1 - Synthesis, structural characterization, DFT calculations and antiproliferative evaluation of novel spirohydantoin derivatives containing a substituted benzyl moiety EP - 62 SP - 48 VL - 1180 DO - 10.1016/j.molstruc.2018.11.071 ER -
@article{ author = "Lazić, Anita M. and Radovanović, Lidija D. and Božić, Bojan Đ. and Božić Nedeljković, Biljana Đ. and Vitnik, Vesna D. and Vitnik, Željko J. and Rogan, Jelena R. and Valentić, Nataša V. and Ušćumlić, Gordana S. and Trišović, Nemanja P.", year = "2019", abstract = "Two series of cycloalkanespiro-5-hydantoins, namely cyclohexanespiro-5-hydantoins and cycloheptanespiro-5-hydantoins with a 4-substituted benzyl or a 2-(4-substituted phenyl)-2-oxoethyl group at N3 position, were synthesized and their effects on proliferation of human colon (HCT-116), leukemia (K562) and breast (MDA-MB-231) cancer cell lines were tested. For comparison, we also described the 5,5-diphenylhydantoin analogues. The structural features of the investigated compounds were characterized by elemental analysis, FT-IR, UV–Vis, 1 H and 13 C NMR spectroscopy and X-ray crystallography. Regarding their structure–activity relationships, it was shown that the substitution on the benzyl moiety with the methoxy, chloro or bromo group potentiated the antiproliferative activity relative to the parent compounds, while an increase in the size of the cycloalkyl group resulted mostly in a decrease of the antiproliferative activity. The single crystal X-ray analysis revealed the existence of dimers and chains formed by the N–H⋯O hydrogen bonds. The analysis of the molecular descriptors of Lipinski demonstrated that all investigated compounds obeyed the rule of five. To further understand their geometry and electronic structure, DFT calculations with B3LYP method using 6-311++G(d,p) basic set were performed. In this context, the UV–Vis spectra of the investigated compounds were analyzed in detail, whereby the predicted absorption spectra from DFT calculation matched the experimentally obtained ones, with a good correlation. The interesting physico-chemical and pharmacologically relevant properties of the investigated compounds warrant their further investigation.", publisher = "Elsevier B.V.", journal = "Journal of Molecular Structure", title = "Synthesis, structural characterization, DFT calculations and antiproliferative evaluation of novel spirohydantoin derivatives containing a substituted benzyl moiety", pages = "62-48", volume = "1180", doi = "10.1016/j.molstruc.2018.11.071" }
Lazić, A. M., Radovanović, L. D., Božić, B. Đ., Božić Nedeljković, B. Đ., Vitnik, V. D., Vitnik, Ž. J., Rogan, J. R., Valentić, N. V., Ušćumlić, G. S.,& Trišović, N. P.. (2019). Synthesis, structural characterization, DFT calculations and antiproliferative evaluation of novel spirohydantoin derivatives containing a substituted benzyl moiety. in Journal of Molecular Structure Elsevier B.V.., 1180, 48-62. https://doi.org/10.1016/j.molstruc.2018.11.071
Lazić AM, Radovanović LD, Božić BĐ, Božić Nedeljković BĐ, Vitnik VD, Vitnik ŽJ, Rogan JR, Valentić NV, Ušćumlić GS, Trišović NP. Synthesis, structural characterization, DFT calculations and antiproliferative evaluation of novel spirohydantoin derivatives containing a substituted benzyl moiety. in Journal of Molecular Structure. 2019;1180:48-62. doi:10.1016/j.molstruc.2018.11.071 .
Lazić, Anita M., Radovanović, Lidija D., Božić, Bojan Đ., Božić Nedeljković, Biljana Đ., Vitnik, Vesna D., Vitnik, Željko J., Rogan, Jelena R., Valentić, Nataša V., Ušćumlić, Gordana S., Trišović, Nemanja P., "Synthesis, structural characterization, DFT calculations and antiproliferative evaluation of novel spirohydantoin derivatives containing a substituted benzyl moiety" in Journal of Molecular Structure, 1180 (2019):48-62, https://doi.org/10.1016/j.molstruc.2018.11.071 . .