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Pregled bibliografske jedinice broj: 1102019

Preclinical in vitro screening of newly synthesised amidino substituted benzimidazoles and benzothiazoles


Racané, Livio; Cindrić, Maja; Zlatar, Ivo; Kezele, Tatjana; Milić, Astrid; Brajša, Karmen; Hranjec, Marijana
Preclinical in vitro screening of newly synthesised amidino substituted benzimidazoles and benzothiazoles // Journal of enzyme inhibition and medicinal chemistry, 36 (2021), 1; 163-174 doi:10.1080/14756366.2020.1850711 (međunarodna recenzija, članak, znanstveni)


CROSBI ID: 1102019 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Preclinical in vitro screening of newly synthesised amidino substituted benzimidazoles and benzothiazoles

Autori
Racané, Livio ; Cindrić, Maja ; Zlatar, Ivo ; Kezele, Tatjana ; Milić, Astrid ; Brajša, Karmen ; Hranjec, Marijana

Izvornik
Journal of enzyme inhibition and medicinal chemistry (1475-6366) 36 (2021), 1; 163-174

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Amidines ; benzimidazoles ; benzotiazoles ; 2D and 3D in vitro cytotoxicity assay ; apoptotic activity ; ADME

Sažetak
Newly synthesised benzimidazole/benzotiazole derivatives bearing amidino, namely 3, 4, 5, 6- tetrahydropyrimidin-1-ium chloride, substituents have been evaluated for their potential antitumor activity in vitro. Compounds and standard drugs (doxorubicin, staurosporine and vandetanib) were tested on three human lung cancer cell lines A549, HCC827 and NCI-H358. We tested compounds in MTS citotoxicity assay and in BrdU proliferative assay performed on 2 D and 3 D assay format. Because benzmidazole scaffold is similar to natural purines, we tested the most active compounds for ability to induce cell apoptosis of A549 by binding to DNA in comparison with doxorubicin and saturosporine. Additionally, the ADME properties of the most active benzothiazole/benzimidazole and non-active compounds were determined to see if the different ADME properties are the cause of different activity in 2 D and 3 D assays, as well as to see if the tested active compounds have drug like properties and potency for further profilation. ADME characterisation included solubility, lipophilicity, permeability, metabolic stability and binding to plasma proteins. In general, the benzothiazole derivatives were more active in comparison to their benzimidazole analogues. The exception was 2-phenyl substituted benzimidazole 6a being active with very pronounced activity especially towards HCC827 cells. All active compounds have similar mode of action on A549 cell line as standard compound doxorubicin, which binds to nucleic acids with the DNA double helix. Tested active benzothiazole compounds were characterised by moderate to good solubility, good metabolic stability, low permeability and high binding to plasma proteins. One tested active benzimidazole derivative showed ADME properties, but lower lipophilicity resulted in low PPB and higher metabolic instability. In addition, no significant difference was observed in ADME profile between active and non-active compounds.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija, Temeljne medicinske znanosti



POVEZANOST RADA


Projekti:
IP-2018-01-4379 - Istraživanje antioksidativnog djelovanja benzazolskog skeleta u dizajnu novih antitumorskih agensa (AntioxPot) (Hranjec, Marijana, HRZZ - 2018-01) ( POIROT)

Ustanove:
Tekstilno-tehnološki fakultet, Zagreb,
Fakultet kemijskog inženjerstva i tehnologije, Zagreb,
Fidelta d.o.o.

Profili:

Avatar Url Karmen Brajša (autor)

Avatar Url Marijana Hranjec (autor)

Avatar Url Astrid Milić (autor)

Avatar Url Maja Cindrić (autor)

Avatar Url Livio Racane (autor)

Citiraj ovu publikaciju

Racané, Livio; Cindrić, Maja; Zlatar, Ivo; Kezele, Tatjana; Milić, Astrid; Brajša, Karmen; Hranjec, Marijana
Preclinical in vitro screening of newly synthesised amidino substituted benzimidazoles and benzothiazoles // Journal of enzyme inhibition and medicinal chemistry, 36 (2021), 1; 163-174 doi:10.1080/14756366.2020.1850711 (međunarodna recenzija, članak, znanstveni)
Racané, L., Cindrić, M., Zlatar, I., Kezele, T., Milić, A., Brajša, K. & Hranjec, M. (2021) Preclinical in vitro screening of newly synthesised amidino substituted benzimidazoles and benzothiazoles. Journal of enzyme inhibition and medicinal chemistry, 36 (1), 163-174 doi:10.1080/14756366.2020.1850711.
@article{article, year = {2021}, pages = {163-174}, DOI = {10.1080/14756366.2020.1850711}, keywords = {Amidines, benzimidazoles, benzotiazoles, 2D and 3D in vitro cytotoxicity assay, apoptotic activity, ADME}, journal = {Journal of enzyme inhibition and medicinal chemistry}, doi = {10.1080/14756366.2020.1850711}, volume = {36}, number = {1}, issn = {1475-6366}, title = {Preclinical in vitro screening of newly synthesised amidino substituted benzimidazoles and benzothiazoles}, keyword = {Amidines, benzimidazoles, benzotiazoles, 2D and 3D in vitro cytotoxicity assay, apoptotic activity, ADME} }
@article{article, year = {2021}, pages = {163-174}, DOI = {10.1080/14756366.2020.1850711}, keywords = {Amidines, benzimidazoles, benzotiazoles, 2D and 3D in vitro cytotoxicity assay, apoptotic activity, ADME}, journal = {Journal of enzyme inhibition and medicinal chemistry}, doi = {10.1080/14756366.2020.1850711}, volume = {36}, number = {1}, issn = {1475-6366}, title = {Preclinical in vitro screening of newly synthesised amidino substituted benzimidazoles and benzothiazoles}, keyword = {Amidines, benzimidazoles, benzotiazoles, 2D and 3D in vitro cytotoxicity assay, apoptotic activity, ADME} }

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