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Updated: Mar 18, 2026
Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis, Molecular Docking Study and in vitro Anticancer Activity of Tetrazole Linked Benzochromene Derivatives
Sridevi Gorle1, Suresh Maddila2, Surya N Maddila3
1Non-viral gene delivery laboratory, Discipline of Biochemistry, School of Life Sciences, University of KwaZulu-Natal, Chiltern Hills, Durban-4000, South Africa.
Background:
Globally, cancer is regarded as one of the biggest health concern in humans and animals and is one of the most terrifying diseases. Therefore, there is a necessity for the discovery, development and improvement of novel antitumor drug molecules which could efficiently prevent proliferative pathways and clonal expansion of cells. Heterocyclic compounds like benzochromene play a key role in the development of current pharmaceuticals, natural resources, agriculture products, analytical reagents and dyes. Therefore, anticancer drugs show increased resistance, it is essential to designing the novel structured heterocyclic moieties to create potential anticancer agents with promising biological applications.
Objective:
To synthesis a novel 1-(substitutedphenyl)-2-(1H-tetrazol-5-yl)-1H-benzo[f]chromene-3-amine derivatives for in vitro antitumour activity.
Method:
The reaction of 3-amino-1-(substitutedphenyl)-1H-benzo[f]chromene-2-carbonitrile with sodium azide, ammonium chloride in dimethyl formamide solvent under reflux condition for 4 h afforded products (3a-k). The synthesized molecules were subjected to possible potential anti-tumour activity in vitro in four human cancer cell lines (MCF-7, Caco-2, HeLa and SKBR-3), and one human non-cancer cell line (HEK293), using the MTT cell viability assay.
Results:
A novel series of products (3a-k) were synthesized with good yield and were identified with 1H NMR, 15N NMR, 13C NMR, FT-IR and HR-MS spectrum. The most potent compounds 3d, 3e, and 3f possessing the greatest cytotoxicity activity with IC50 values slightly higher (15-33 μM) than that of 5-Fluorouracil (10-17 μM), indicating their potential to be antitumor agents. The 3a, 3b, 3c, 3h, 3i and 3j compounds showed moderate activity. Additionally, a molecular docking analysis was conducted to predict the multi-drug resistance modulator behavior of synthesized compounds in the ATP binding site of P-glycoprotein.
Conclusions:
We synthesized and designated eleven novel derivatives of tetrazole linked benzochromenes (3a-k) and evaluated their anti-cancer activity. Additionally, the results from the docking studies were found to be in good agreement with the results from computational profiling.
Insights
Novel tetrazole-linked benzochromene derivatives were synthesized and tested for anticancer activity. Compounds 3d, 3e, and 3f showed promising cytotoxicity against human cancer cell lines, indicating potential as new antitumor agents.
Area of Science:
- Medicinal Chemistry
- Organic Synthesis
- Pharmacology
Background:
- Cancer remains a significant global health concern, necessitating novel antitumor drug discovery.
- Heterocyclic compounds, such as benzochromenes, are crucial scaffolds in pharmaceutical development.
- Developing novel anticancer agents is essential due to increasing drug resistance.
Purpose of the Study:
- To synthesize novel 1-(substitutedphenyl)-2-(1H-tetrazol-5-yl)-1H-benzo[f]chromene-3-amine derivatives.
- To evaluate the in vitro antitumour activity of these novel derivatives.
Main Methods:
- Synthesis of eleven novel tetrazole-linked benzochromene derivatives (3a-k) via a multi-step reaction.
- Characterization of synthesized compounds using spectroscopic techniques (1H NMR, 15N NMR, 13C NMR, FT-IR, HR-MS).
- In vitro cytotoxicity assessment using the MTT assay against human cancer cell lines (MCF-7, Caco-2, HeLa, SKBR-3) and a non-cancer cell line (HEK293).
Main Results:
- Successful synthesis and characterization of eleven novel benzochromene derivatives with good yields.
- Compounds 3d, 3e, and 3f exhibited potent cytotoxicity with IC50 values in the range of 15-33 μM.
- Molecular docking analysis predicted multi-drug resistance modulator behavior at the P-glycoprotein ATP binding site.
Conclusions:
- Eleven novel tetrazole-linked benzochromene derivatives were synthesized and evaluated for anticancer potential.
- Compounds 3d, 3e, and 3f demonstrated significant in vitro antitumor activity.
- Docking studies supported the computational profiling and potential therapeutic applications of these compounds.
