Design, Synthesis of New 1,2,4-Triazole/1,3,4-Thiadiazole with Spiroindoline, Imidazo[4,5-b]quinoxaline and Thieno[2,3-d]pyrimidine from Isatin Derivatives as Anticancer Agents.

Ameen Ali Abu-Hashem,Sami A Al-Hussain

doi:10.3390/molecules27030835

Abstract

The current work aims to design and synthesis a new series of isatin derivatives and greatly enhances their cytotoxic activity. The derivatives 3-((bromophenyl) imino)-1-(morpholino (pyridine) methyl) indolin-2-one, 2-((oxoindoline) amino) benzoic acid, 3-(thiazolo-imino) indolinone, ethyl-2-((oxoindolin-3-ylidene)amino)-benzothiophene-3-carboxylate, 1-(oxoindoline)-benzo[4,5] thieno [2,3-d]pyrimidin-4(1H)-one, ethyl-2-(2-oxoindoline) hydrazine-1-carboxylate, N-(mercapto-oxo-pyrimidine)-2-(oxoindoline) hydrazine-1-carboxamide, N-(oxo-thiazolo[3,2-a] pyrimidine)-2-(oxoindolin-ylidene) hydrazine-carboxamide, 3-((amino-phenyl) amino)-3-hydroxy- indolinone, 3-((amino-phenyl) imino)-indolinone, 2-(2-((oxoindoline) amino) phenyl) isoindolinone, 2-(oxoindoline) hydrazine-carbothioamide, 5′-thioxospiro[indoline-3,3′-[1,2,4]triazolidin]-one, 5′-amino-spiro[indoline-3,2′-[1,3,4]thiadiazol]-2-one and 3-((2-thioxo-imidazo[4,5-b]quinoxaline) imino) indolinone were synthesized from the starting material 1-(morpholino (pyridine) methyl) indoline-2,3-dione and evaluated for their in vitro cytotoxic activity against carcinogenic cells. The new chemical structures were evidenced using spectroscopy (IR, NMR and MS) and elemental analysis. The results show that compounds imidazo[4,5-b]quinoxaline-indolinone, thiazolopyrimidine-oxoindoline, pyrimidine-oxoindoline-hydrazine-carboxamide, spiro[indoline-3,2′-[1,3,4] thiadiazol]-one and spiro[indoline-3,3′-[1,2,4]triazolidin]-one have excellent anti-proliferative activities against different human cancer cell lines such as gastric carcinoma cells (MGC-803), breast adenocarcinoma cells (MCF-7), nasopharyngeal carcinoma cells (CNE2) and oral carcinoma cells (KB).

Highlights

Cancer has been spreading among people at a high rate
Many studies have been demonstrating the synthesis of spiro derivatives of isatin at the (C-3) position as α-methylene γ-butyrolactone spirocyclic, which is derived from isatin and is the proper core for optimization to identify new anticancer agents [4]
The IR spectrum compound (2) showed absorption bands at ν 1735 and 1680 cm−1 conforming to two carbonyl groups. 1H-NMR spectrums of (2) revealed multiplet signals at δ 2.60–3.05 ppm corresponding to eight protons of morpholine and one singlet at δ 6.72 ppm corresponding to one proton of methine proton

Summary

Introduction

Cancer is one of the main causes of death. In 2017, the death of nearly 9.6 million people due to different types of cancer made it the second leading cause of death, second only to cardiovascular diseases [1,2]. In the last decade, many researchers have worked to prepare various heterocyclic compounds that are used in the treatment of most cancer cells in the human body. Isatin derivatives are an interesting category of heterocyclic molecules that have different biological and pharmacological activities [3]. Spiro compounds have been showing distinguished pharmacological activity, especially in the chemistry of natural products. The spiro pyrazole-oxindole analogues are considered as valuable anticancer agents against human cancer cells [5]

Methods

Results

Conclusion