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Updated: Oct 15, 2025
Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Antiproliferative, apoptosis-inducing activity and molecular docking studies of sydnones compounds
Syed Lidia Hossain1, Manoj Mathews2, Veerabhadra Swamy Bhyranalyar Nagarajappa3
1Department of Biotechnology, Sir M Visvesvaraya Institute of Technology, Bengaluru, India.
Objective:
To evaluate the antiproliferative and apoptosis inducing activity of different sydnones on cancer cell lines and their interaction with cancer proteins by molecular docking studies.
Material And Methods:
Antiproliferative activity was carried out by MTT assay and apoptosis inducing activity was performed by DAPI and Annexin V and propidium iodide staining. Molecular docking studies were performed using AutoDock Tools 1.5.6. Pharmacokinetics properties like ADME and toxicity were analysed by pkCSM web server.
Result:
In this study, four new sydnone compounds 3-(4-nonylbiphenyl-4'-yl) sydnone (MC-182), 3-(4-propylbiphenyl-4'-yl) sydnone (MC-454), 3-(4-hexylbiphenyl-4'-yl) sydnone (MC-433), and 3-(4-methylbiphenyl-4'-yl) sydnone (MC-431) were screened for antiproliferative and apoptotic effect against BT-474 (human breast cancer), HeLa (human cervical cancer) and Jurkat (human myeloid leukemia) Mostly, all the sydnone compounds exhibited decent antiproliferative effectiveness, but compound MC-431, MC-433, and MC-454 showed more antiproliferative activity (IC50 1.71, 10.09 and 2.87 μM against BT-474, Hela and Jurkat cell line, respectively). The changes of morphological characteristics of cancer cells determined by staining techniques indicate the apoptotic cell death. The molecular docking and interaction studies were carried out between sydnones with cancer proteins (epidermal growth factor domain receptor tyrosine kinase [EGF-TK], tumor necrosis factor-alpha [TNF-α] and Caspase3. Among all four sydnone molecules, two compounds MC-454 and MC-431 showed good binding energy with targeted proteins. Drug-like property was predicted by ADME toxicity study.
Conclusion:
The results indicate sydnone compounds were found to exhibit anticancer activity by inducing apoptosis. The molecular docking study of sydnones with cancer proteins showed a decent interaction affinity. The results of absorption, distribution, metabolism, excretion and toxicity studies by the Insilco approach also proved that MC-454 sydnone showed better In-Vivo administration. Thus, the current research work indicates that these sydnone compounds would be prospective in developing anticancer medicines.
Insights
Four novel sydnone compounds demonstrated significant anticancer properties by inducing apoptosis in cancer cells. Molecular docking and ADME studies suggest MC-454 is a promising candidate for developing new anticancer drugs.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Molecular Biology
Background:
- Cancer remains a leading cause of mortality worldwide, necessitating the development of novel therapeutic agents.
- Sydnone derivatives have emerged as a class of compounds with potential biological activities.
- Understanding the antiproliferative and apoptotic mechanisms of novel compounds is crucial for drug discovery.
Purpose of the Study:
- To evaluate the antiproliferative and apoptosis-inducing effects of four novel sydnone compounds against human cancer cell lines.
- To investigate the molecular interactions of these sydnones with key cancer-related proteins using molecular docking.
- To assess the drug-like properties, including ADME (absorption, distribution, metabolism, excretion) and toxicity, of the synthesized sydnones.
Main Methods:
- Antiproliferative activity was assessed using the MTT assay.
- Apoptosis induction was evaluated through DAPI, Annexin V, and propidium iodide staining.
- Molecular docking studies were performed using AutoDock Tools to predict binding affinities with target proteins (EGF-TK, TNF-α, Caspase3).
- Pharmacokinetic properties and toxicity were analyzed using the pkCSM web server.
Main Results:
- Compounds MC-431, MC-433, and MC-454 exhibited significant antiproliferative activity against BT-474, HeLa, and Jurkat cell lines, with IC50 values as low as 1.71 μM.
- Morphological changes observed via staining confirmed apoptosis induction in treated cancer cells.
- Molecular docking revealed favorable binding energies for MC-454 and MC-431 with target proteins, indicating potential therapeutic interactions.
- In silico ADME/toxicity predictions suggested MC-454 possesses favorable properties for in vivo administration.
Conclusions:
- The studied sydnone compounds demonstrate potent anticancer activity through apoptosis induction.
- Molecular docking studies confirm the potential of these sydnones to interact with critical cancer targets.
- MC-454, in particular, shows promise as a lead compound for the development of novel anticancer therapeutics due to its efficacy and favorable predicted pharmacokinetic profile.
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