Investigation of the Effects of Benzimidazole Derivatives on the mTOR Pathway in Breast Cancer

Ronak Haj Ersan

Makale detayları

Investigation of the Effects of Benzimidazole Derivatives on the mTOR Pathway in Breast Cancer

Yazarlar:

Ronak Haj Ersan

Yayıncı:

Erzincan Binali Yildirim University

Ana Başlıklar:

Farmasotik Kimya

Dergi:

Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.18 Issue 2, pp.361-371

Belge Tipi:

Makale

Yayın Tarihi:

8/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001356187

pISSN:

2149-4584

Anahtar kelimeler:

Özet:

 The mammalian target of rapamycin mTOR pathway plays a critical role in cancer progression, making it a key target for therapeutic intervention. Dysregulation of mTOR signaling is frequently observed in malignancies, highlighting the need for potent and selective inhibitors. In this study, a series of benzimidazole derivatives were designed and evaluated for their potential as mTOR inhibitors. Cytotoxicity assessments using MTT assays demonstrated that compounds 10 and 15 exhibited significant anti-proliferative effects against breast cancer cell lines, with IC₅₀ values of 6.63 µM and 5.28 µM, respectively. Further biochemical studies revealed that the most active compounds effectively suppressed mTOR phosphorylation at Ser2448 in MCF-7 cells, as confirmed by colorimetric enzymatic activity assays. These results suggest that compound 15, in particular, represents a promising lead for the development of novel mTOR-targeted therapies. This study provides valuable insights into the structure-based design of mTOR inhibitors, offering a foundation for future advancements in targeted cancer treatment.

 The mammalian target of rapamycin mTOR pathway plays a critical role in cancer progression, making it a key target for therapeutic intervention. Dysregulation of mTOR signaling is frequently observed in malignancies, highlighting the need for potent and selective inhibitors. In this study, a series of benzimidazole derivatives were designed and evaluated for their potential as mTOR inhibitors. Cytotoxicity assessments using MTT assays demonstrated that compounds 10 and 15 exhibited significant anti-proliferative effects against breast cancer cell lines, with IC₅₀ values of 6.63 µM and 5.28 µM, respectively. Further biochemical studies revealed that the most active compounds effectively suppressed mTOR phosphorylation at Ser2448 in MCF-7 cells, as confirmed by colorimetric enzymatic activity assays. These results suggest that compound 15, in particular, represents a promising lead for the development of novel mTOR-targeted therapies. This study provides valuable insights into the structure-based design of mTOR inhibitors, offering a foundation for future advancements in targeted cancer treatment.

 The mammalian target of rapamycin mTOR pathway plays a critical role in cancer progression, making it a key target for therapeutic intervention. Dysregulation of mTOR signaling is frequently observed in malignancies, highlighting the need for potent and selective inhibitors. In this study, a series of benzimidazole derivatives were designed and evaluated for their potential as mTOR inhibitors. Cytotoxicity assessments using MTT assays demonstrated that compounds 10 and 15 exhibited significant anti-proliferative effects against breast cancer cell lines, with IC₅₀ values of 6.63 µM and 5.28 µM, respectively. Further biochemical studies revealed that the most active compounds effectively suppressed mTOR phosphorylation at Ser2448 in MCF-7 cells, as confirmed by colorimetric enzymatic activity assays. These results suggest that compound 15, in particular, represents a promising lead for the development of novel mTOR-targeted therapies. This study provides valuable insights into the structure-based design of mTOR inhibitors, offering a foundation for future advancements in targeted cancer treatment.

 Rapamisin memeli hedefi mTOR sinyal yolu, kanser ilerlemesinde kritik bir rol oynayarak terapötik müdahaleler için önemli bir hedef haline gelmiştir. mTOR sinyal iletiminin düzensizliği, malignitelerde sıkça gözlemlenmekte olup, güçlü ve seçici inhibitörlere olan ihtiyacı vurgulamaktadır. Bu çalışmada, bir dizi benzimidazol türevi tasarlanmış ve potansiyel mTOR inhibitörleri olarak değerlendirilmiştir. MTT analizleri ile yapılan sitotoksisite değerlendirmeleri, 10 ve 15 numaralı bileşiklerin meme kanseri hücre hatlarına karşı belirgin anti-proliferatif etki gösterdiğini ortaya koymuş ve IC₅₀ değerleri sırasıyla 6,63 µM ve 5,28 µM olarak belirlenmiştir. Biyokimyasal incelemeler, en aktif bileşiklerin MCF-7 hücrelerinde Ser2448 bölgesinde mTOR fosforilasyonunu etkili bir şekilde baskıladığını ve bu durumun kolorimetrik enzim aktivite testleriyle doğrulandığını göstermiştir. Elde edilen bulgular, özellikle 15 numaralı bileşiğin yeni mTOR hedefli tedavilerin geliştirilmesi için umut verici bir öncü olabileceğini ortaya koymaktadır. Bu çalışma, mTOR inhibitörlerinin yapı bazlı tasarımına dair değerli bilgiler sunarak hedefe yönelik kanser tedavilerinin gelecekteki gelişmelere katkı sağlayacaktır.

Makale detayları

Investigation of the Effects of Benzimidazole Derivatives on the mTOR Pathway in Breast Cancer

Yazarlar:

Ronak Haj Ersan

Yayıncı:

Erzincan Binali Yildirim University

Ana Başlıklar:

Farmasotik Kimya

Dergi:

Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.18 Issue 2, pp.361-371

Belge Tipi:

Makale

Yayın Tarihi:

8/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001356187

pISSN:

2149-4584

Benzimidazole

mTOR inhibitory activity

structure-activity relationshipBenzimidazol

mTOR inhibitör aktivite

yapı-aktivite ilişkisi

Sayı

Makale detayları

Investigation of the Effects of Benzimidazole Derivatives on the mTOR Pathway in Breast Cancer

Yazarlar: Ronak Haj Ersan

Yayıncı: Erzincan Binali Yildirim University

Ana Başlıklar: Farmasotik Kimya

Dergi: Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.18 Issue 2, pp.361-371

Belge Tipi: Makale

Yayın Tarihi: 8/2025

Belge Dili: İngilizce

Document ID (Org No.): 2001356187

pISSN: 2149-4584

Benzimidazole

mTOR inhibitory activity

structure-activity relationshipBenzimidazol

mTOR inhibitör aktivite

yapı-aktivite ilişkisi

Sayı

Yazarlar:

Ronak Haj Ersan

Yayıncı:

Erzincan Binali Yildirim University

Ana Başlıklar:

Farmasotik Kimya

Dergi:

Erzincan Üniversitesi Fen Bilimleri Enstitüsü Dergisi Vol.18 Issue 2, pp.361-371

Belge Tipi:

Makale

Yayın Tarihi:

8/2025

Belge Dili:

İngilizce

Document ID (Org No.):

2001356187

pISSN:

2149-4584