Anticancer Effect and Safety Profile of a 4-Pyridyl Linked Triazolotriazine Derivative against Colorectal Tumor

Document Type : Original Research Articles

Authors
Reyhaneh Monfared 1
Soghra Farzipour 2
Sakineh Dadashpour 3
Zahra Zakeri Khatir 1
Seyed Jalal Hosseinimehr 3
Fereshteh Talebpour Amiri 4
Hamid Irannejad 1
1 1 Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Islamic Republic of Iran
2 2 Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Islamic Republic of Iran
3 3 Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Islamic Republic of Iran
4 4 Department of Anatomy, Faculty of Medicine, Molecular and Cell Biology Research Center, Mazandaran University of Medical Sciences, Sari, Islamic Republic of Iran
10.22059/jsciences.2023.366069.1007830
Abstract
Cancer is the second leading cause of global death, and colorectal cancer is the fourth most common cancer worldwide. In this study, the anticancer effect and safety profile of a 3-(pyridyl-4-l-methylthio) triazolotriazine derivative (10b) was investigated. The anti-tumor activity of 10b was evaluated on HT-29 human colon cancer cell. To confirm the in vivo anti-cancer effect of 10b, human colon tumor xenograft mice was used. Tumor bearing mice were treated with 10b and paclitaxel for 10 days, then were sacrificed and their heart, liver and tumor tissues were isolated for pathological evaluation. Mice weight and tumor size were measured daily, and mortality was recorded. The results of cellular experiments showed that IC50 of paclitaxel and 10b was 0.34 and 8.92 µM after 72 hours, respectively. The results of measuring the weight of mice and tumor size didn't show any significant changes in the 10b treated groups. Pathological examinations indicated that the extent of hepatotoxicity and cardiac toxicity in mice receiving 10b was lower than that of the paclitaxel group. Interestingly and hopefully, all mice treated with 10b remained alive during the experiment but 50% of mice treated with paclitaxel and also 50% of mice in the control group were died. Totally, 10b showed acceptable in vitro anti-tumor activity on HT-29 colorectal cells and no mortality in this group confirms the safety profile of 10b.
Keywords
Colorectal cancer
Triazolotriazine
Tumor
HT-29
Xenograft
Subjects
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Journal of Sciences, Islamic Republic of Iran
Volume 34, Issue 3
Summer 2023
Pages 217-226