Synthesis, in silico and in vitro anti-proliferative studies of some novel benzamido substituted imidazo[1,2-b]pyridazin-2-ones

Kanna Sruthı; Mogili Sumakanth; Kumar CB Mahendra; Kondapalli Naresh

doi:10.1501/Eczfak_0000000591

BAZI YENİ BENZAMİDO SÜBSTİTÜE İMİDAZO[1,2-b]PİRİDAZİN-2-ON BİLEŞİKLERİNİN SENTEZİ, İN SİLİKO VE İN VİTRO ANTİ- PROLİFERATİF ÇALIŞMALARI

Year 2017, Volume: 41 Issue: 1, 10 - 25, 01.05.2017

Kanna Sruthı Mogili Sumakanth Kumar CB Mahendra Kondapalli Naresh

https://doi.org/10.1501/Eczfak_0000000591

Abstract

Yeni bir seri benzamido sübstitüe imidazo[1,2-b]piridazin-2-on bileşikleri tasarlanmış, sentezlenmiş ve
olası anti-proliferatif etkisi test edilmiştir. Bu bileşikler, çeşitli 4-arilidin-2-feniloksazol-5-on bileşiklerinin
etilen glikol varlığında 3-aminopiridazin ile reaksiyona sokulmasıyla gerçekleştirilmiştir. Sentezlenen
bileşiklerin kimyasal yapıları IR, 1H NMR, 13C NMR, Kütle spektrumu ve elemental analiz ile karakterize
edilmiştir. Sentezlenen bileşikler, insan kanser hücre hatları A375 ve Colo-205 üzerinde olası anti-proliferatif
etkileri açısından MTT testi ile değerlendirilmiştir. Test edilen bileşikler arasında bileşik 6m ve 6n her iki hücre
hattı üzerinde güçlü anti-proliferatif etki göstermiş ve bileşik 6i, 6g ve 6d de önemli bir etki göstermiştir. OSIRIS
Property Explorer programı ile bileşik 6a-6n için moleküler özellikleri ve toksisitesi tahmin edilmiştir. Test
edilen tüm bileşiklerin, ilaç olmaya aday olduğu kanıtlanmış ve toksisite ve teratojeniteden arındırılmıştır.
Sentezlenen 6a-6n bileşiklerinin B-Raf V600E kinaz (PDB ID: 3IDP) üzerine yapılan moleküler doking
çalışmaları, aktif bölgeye bağlanan aktif bileşiklerin Cys532, Phe595, Lys483 aminoasit kalıntılarıyla
etkileşimleri ile Dabrafenib'in etkileşimlerinin karşılaştırılabilir olduğunu ortaya koymuştur. Bu çalışmalar,
imidazo[1,2-b]piridazin benzamitlerin umut verici anti-proliferatif ajanlar kapsamını genişletmiştir.

Keywords

anti-proliferatif ajanlar, B-Raf V600E kinase, benzamidler, imidazopiridazinler

Synthesis, in silico and in vitro anti-proliferative studies of some novel benzamido substituted imidazo[1,2-b]pyridazin-2-ones

Year 2017, Volume: 41 Issue: 1, 10 - 25, 01.05.2017

Kanna Sruthı Mogili Sumakanth Kumar CB Mahendra Kondapalli Naresh

https://doi.org/10.1501/Eczfak_0000000591

Abstract

ted for their possible anti-proliferative activity. The title compounds were accomplished by the reaction of
various 4-Arylidine-2-Phenyl-Oxazol-5-Ones with 3-Aminopyridazine in the presence of ethylene glycol. The
chemical structures of the synthesized compounds was characterised by IR, 1H NMR, 13C NMR, Mass spectra
and elemental analysis. The synthesized compounds were evaluated for their possible anti-proliferative activity
on human cancer cell lines A375 and Colo-205 using MTT assay. Among the tested compounds, compound 6m
and 6n showed potent anti-proliferative activity on both cell lines and compounds 6i, 6g and 6d also
demonstrated significant activity. Molecular properties and toxicity were predicted for compounds 6a-6n with
OSIRIS property explorer. All the tested compounds were proved to be druggable candidates and free from
toxicity and teratogenecity. The molecular docking studies of synthesized compounds 6a-6n on B-Raf V600E
kinase (PDB ID: 3IDP) further revealed that the active compounds bound to the active site and interacting with
Cys532, Phe595, Lys483 residues are comparable with the interactions of Dabrafenib. These studies broadened
the scope of imidazo[1,2-b]pyridazine benzamides as promising antiproliferative agents.

Keywords

anti-proliferative agents, benzamides, B-Raf V600E kinase, imidazopyridazines

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Details

Other ID	JA98NB85CB
Journal Section	Research Article
Authors	Kanna Sruthı This is me Mogili Sumakanth This is me Kumar CB Mahendra This is me Kondapalli Naresh This is me
Publication Date	May 1, 2017
Submission Date	May 1, 2017
Published in Issue	Year 2017 Volume: 41 Issue: 1

Cite

APA	Sruthı, K., Sumakanth, M., Mahendra, K. C., Naresh, K. (2017). Synthesis, in silico and in vitro anti-proliferative studies of some novel benzamido substituted imidazo[1,2-b]pyridazin-2-ones. Journal of Faculty of Pharmacy of Ankara University, 41(1), 10-25. https://doi.org/10.1501/Eczfak_0000000591
AMA	Sruthı K, Sumakanth M, Mahendra KC, Naresh K. Synthesis, in silico and in vitro anti-proliferative studies of some novel benzamido substituted imidazo[1,2-b]pyridazin-2-ones. J. Fac. Pharm. Ankara. May 2017;41(1):10-25. doi:10.1501/Eczfak_0000000591
Chicago	Sruthı, Kanna, Mogili Sumakanth, Kumar CB Mahendra, and Kondapalli Naresh. “Synthesis, in Silico and in Vitro Anti-Proliferative Studies of Some Novel Benzamido Substituted imidazo[1,2-b]pyridazin-2-Ones”. Journal of Faculty of Pharmacy of Ankara University 41, no. 1 (May 2017): 10-25. https://doi.org/10.1501/Eczfak_0000000591.
EndNote	Sruthı K, Sumakanth M, Mahendra KC, Naresh K (May 1, 2017) Synthesis, in silico and in vitro anti-proliferative studies of some novel benzamido substituted imidazo[1,2-b]pyridazin-2-ones. Journal of Faculty of Pharmacy of Ankara University 41 1 10–25.
IEEE	K. Sruthı, M. Sumakanth, K. C. Mahendra, and K. Naresh, “Synthesis, in silico and in vitro anti-proliferative studies of some novel benzamido substituted imidazo[1,2-b]pyridazin-2-ones”, J. Fac. Pharm. Ankara, vol. 41, no. 1, pp. 10–25, 2017, doi: 10.1501/Eczfak_0000000591.
ISNAD	Sruthı, Kanna et al. “Synthesis, in Silico and in Vitro Anti-Proliferative Studies of Some Novel Benzamido Substituted imidazo[1,2-b]pyridazin-2-Ones”. Journal of Faculty of Pharmacy of Ankara University 41/1 (May 2017), 10-25. https://doi.org/10.1501/Eczfak_0000000591.
JAMA	Sruthı K, Sumakanth M, Mahendra KC, Naresh K. Synthesis, in silico and in vitro anti-proliferative studies of some novel benzamido substituted imidazo[1,2-b]pyridazin-2-ones. J. Fac. Pharm. Ankara. 2017;41:10–25.
MLA	Sruthı, Kanna et al. “Synthesis, in Silico and in Vitro Anti-Proliferative Studies of Some Novel Benzamido Substituted imidazo[1,2-b]pyridazin-2-Ones”. Journal of Faculty of Pharmacy of Ankara University, vol. 41, no. 1, 2017, pp. 10-25, doi:10.1501/Eczfak_0000000591.
Vancouver	Sruthı K, Sumakanth M, Mahendra KC, Naresh K. Synthesis, in silico and in vitro anti-proliferative studies of some novel benzamido substituted imidazo[1,2-b]pyridazin-2-ones. J. Fac. Pharm. Ankara. 2017;41(1):10-25.

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The Journal of Faculty of Pharmacy of Ankara University is an international medium, an open access, peer-reviewed journal for the publication of original research reports, reviews and short communications in English or Turkish on relevant developments in pharmaceutical sciences., Proceeding of scientific meetings may be published as special issues of supplements to the journal. Additionally, it contains previous and forthcoming national and international scientific meetings with social activities in pharmaceutical areas.