Design and antiproliferative and antioxidant activities of furan-based thiosemicarbazides and 1,2,4-triazoles: their structure-activity relationship and SwissADME predictions

Yusuf Sicak

doi:10.1007/s00044-021-02756-z

Abstract

Due to the limited number of drugs in current clinical use, the diverse biological applications of furan have encouraged the preparation of a wide variety of thiosemicarbazide and triazole derivatives for the purpose of developing new drug agents. This study aimed to investigate the antiproliferative and antioxidant activities of thiosemicarbazides (1–12) and 1,2,4-triazoles (13–24). Out of the synthesized target compounds, 3, 4, 6, 7, 8, 9, 10, 11, 12, 15, 16, 18, 19, 20, 21, 22, 23, and 24 are novel while the synthesis of the remaining compounds is present in the literature. Compound 15 (IC50: 8.81 ± 0.28 µM) showed the highest antiproliferative activity against the cervical (HeLa) cancer cell line among the compounds. In the lipid peroxidation inhibitory activity, thiosemicarbazide derivatives 3, 10, and 9 showed highest activity with IC50 of 21.80 ± 0.69, 26.49 ± 0.61, and 29.07 ± 0.52 µM, respectively, while triazole derivatives 15, 18, 19, 20, 21, and 22 exhibited the highest activity. Moreover, physicochemical properties, pharmacokinetic properties, and drug-likeness of all synthesized products were calculated using SwissADME. In addition, the effect of the structure–activity relationships of the 1,2,4-triazole derivatives (13–24) on the results of antiproliferative and antioxidant activity assays was evaluated.

Highlights

Cancer, which has been one of the world's biggest health problems for many years, is a malignant disease of the cell cycle that involves uncontrollable mitosis of abnormal cells, which invade surrounding tissues and often spread to other parts of the body [1, 2]
In this study aimed to investigate the antiproliferative and antioxidant activities of some thiosemicarbazides (1-12) and 1,2,4-triazoles (13-24)
The cervical cancer cell line known as highest antiproliferative activity against the cervical (HeLa), which was taken from Henrietta Lack, who passed away in 1951, is the oldest and most common cell line affecting women worldwide and cervical cancer ranks fourth in terms of both incidence and mortality [5, 6]

Summary

Introduction

Cancer, which has been one of the world's biggest health problems for many years, is a malignant disease of the cell cycle that involves uncontrollable mitosis of abnormal cells, which invade surrounding tissues and often spread to other parts of the body [1, 2]. The main treatments of the disease are surgery and radiotherapy. In the many clinical studies on cervical cancer, satisfactory results have been obtained with chemotherapy such as increasing the five-year survival rate of patients [7, 8]. Since the incidence of cervical cancer is at an undeniable level in young women, chemotherapeutic agents are needed [9]. The problem of toxicity and resistance of cancer cells to anticancer agents has led to a continuous search for new chemotherapy agents. High amounts of reactive oxygen species (ROS) have been reported to promote many aspects of tumor development and progression in almost all types of cancer [12]

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Conclusion