Synthesis, cytotoxic assessment, and molecular docking studies of 2,6-diaryl-substituted pyridine and 3,4- dihydropyrimidine-2(1H)-one scaffolds

Zahra HOSSEINZADEH; Nima RAZZAGHI-ASL; Ali RAMAZANI; Hamideh AGHAHOSSEINI; Ali RAMAZANI

Makale detayları

Synthesis, cytotoxic assessment, and molecular docking studies of 2,6-diaryl-substituted pyridine and 3,4- dihydropyrimidine-2(1H)-one scaffolds

Yazarlar:

Zahra HOSSEINZADEH | Nima RAZZAGHI-ASL | Ali RAMAZANI | Hamideh AGHAHOSSEINI | Ali RAMAZANI

Yayıncı:

TUBITAK

Ana Başlıklar:

Uygulamalı fizik

Dergi:

Turkish Journal of Chemistry 2020 Vol.44 Issue 1, pp.194-213

Belge Tipi:

Makale

Yayın Tarihi:

2/2020

Belge Dili:

İngilizce

Document ID (Org No.):

2000725502

Sıklık:

İki Aylık

eISSN:

1303-6130

pISSN:

1300-0527

Özet:

 

Cancer is one of the main global health problems. In order to develop novel antitumor agents, we synthesized 3,4-dihydropyrimidine-2(1H)-one (DHPM) and 2,6-diaryl-substituted pyridine derivatives as potential antitumor structures and evaluated their cytotoxic effects against several cancer cell lines. An easy and convenient method is reported for the synthesis of these derivatives, employing cobalt ferrite (CoFe2 O4 @SiO2 -SO3 H) magnetic nanoparticles under microwave irradiation and solvent-free conditions. The structural characteristics of the prepared nanocatalyst were investigated by FTIR, XRD, SEM, and TGA techniques. In vitro cytotoxic effects of the synthesized products were assessed against the human breast adenocarcinoma cell line (MCF-7), gastric adenocarcinoma (AGS), and human embryonic kidney (HEK293) cells via MTT assay. The results indicated that compound 4r (DHPM derivative) was the most toxic molecule against the MCF-7 cell line (IC50 of 0.17 ?g/mL). Moreover, compounds 4j and 4r (DHPM derivatives) showed excellent cytotoxic activities against the AGS cell line, with an IC50 of 4.90 and 4.97 μg/mL, respectively. Although they are pyridine derivatives, compounds 5g and 5m were more active against the MCF-7 cell line. Results showed that the candidate compounds exhibited low cytotoxicity against HEK293 cells. The kinesin Eg5 inhibitory potential of the candidate compounds was evaluated by molecular docking. The docking results showed that, among the pyridine derivatives, compound 5m had the most free energy of binding (-9.52 kcal/mol) and lowest Ki (0.105 μ4ct with the Eg5 binding site via H-bond interactions to GLU116 and GLY117 residues. The results of our study strongly suggest that DHPM and pyridine derivatives inhibit important tumorigenic features of breast and gastric cancer cells. Our results may be helpful in the further design of DHPMs and pyridine derivatives as potential anticancer agents.

Makale detayları

Synthesis, cytotoxic assessment, and molecular docking studies of 2,6-diaryl-substituted pyridine and 3,4- dihydropyrimidine-2(1H)-one scaffolds

Yazarlar: Zahra HOSSEINZADEH | Nima RAZZAGHI-ASL | Ali RAMAZANI | Hamideh AGHAHOSSEINI | Ali RAMAZANI

Yayıncı: TUBITAK

Ana Başlıklar: Uygulamalı fizik

Dergi: Turkish Journal of Chemistry 2020 Vol.44 Issue 1, pp.194-213

Belge Tipi: Makale

Yayın Tarihi: 2/2020

Belge Dili: İngilizce

Document ID (Org No.): 2000725502

Sıklık: İki Aylık

eISSN: 1303-6130

pISSN: 1300-0527

Sayı

Yazarlar:

Zahra HOSSEINZADEH | Nima RAZZAGHI-ASL | Ali RAMAZANI | Hamideh AGHAHOSSEINI | Ali RAMAZANI

Yayıncı:

TUBITAK

Ana Başlıklar:

Uygulamalı fizik

Dergi:

Turkish Journal of Chemistry 2020 Vol.44 Issue 1, pp.194-213

Belge Tipi:

Makale

Yayın Tarihi:

2/2020

Belge Dili:

İngilizce

Document ID (Org No.):

2000725502

Sıklık:

İki Aylık

eISSN:

1303-6130

pISSN:

1300-0527