Computational investigations and molecular dynamics simulations envisioned for potent antioxidant and anticancer
Sanjai Kumar Yadav1, Ramesh Kumar Yadav2, Umesh Yadava1
1Department of Physics, DDU Gorakhpur University, Gorakhpur, 273009, India.
Abstract:
Cancer, also called malignancy, is a disease which is closely related with the oxidative stress instigated by the overproduction of vulnerable oxygen and nitrogen species. Available drugs are relatively painful and toxic and so are trailing their captivation. Keeping this in mind, we have attempted to reach a novel anti-cancer drug by taking a set of nineteen ligands which are hybrids of Indole-chalcone and triazole. These ligands were allowed to interact with the DNA dodecamer 5'(CGCGAATTCGCG)3' one by one using various docking protocols of Glide. Better docked complexes screened through docking scores and reported activity data were selected and exposed to molecular dynamics run of 20 ns. The dynamical pathways were investigated for each complex comparing the pre- and post- dynamics run. The outcome of the work is discussed in this paper. Among the better hybrids of this series, one of the molecules has shown interesting features, confirming its non-toxic nature and working as intercalator as well minor groove binder, perhaps making it suitable as a potent drug for further pharmacological use.
Insights
Researchers developed novel indole-triazole hybrid ligands as potential anti-cancer drugs. One compound showed promise as a non-toxic intercalator and minor groove binder, suitable for further drug development.
Area of Science:
- Medicinal Chemistry
- Computational Drug Design
- Molecular Biology
Background:
- Cancer is linked to oxidative stress from reactive oxygen and nitrogen species.
- Current anti-cancer drugs often exhibit significant toxicity and side effects.
- There is a need for novel, safer, and effective anti-cancer therapeutic agents.
Purpose of the Study:
- To design and identify novel anti-cancer drug candidates.
- To investigate the interaction of indole-triazole hybrid ligands with DNA.
- To evaluate the potential of these ligands as non-toxic anti-cancer agents.
Main Methods:
- Synthesis of nineteen indole-chalcone-triazole hybrid ligands.
- Molecular docking studies using Glide to assess ligand-DNA interactions.
- 20 ns molecular dynamics simulations to analyze complex stability and dynamics.
- Screening based on docking scores and activity data.
Main Results:
- Several hybrid ligands demonstrated favorable interactions with the DNA dodecamer.
- Molecular dynamics simulations provided insights into the binding mechanisms.
- One specific hybrid molecule exhibited characteristics of a non-toxic intercalator and minor groove binder.
Conclusions:
- The developed indole-triazole hybrid ligands represent a promising class of anti-cancer drug candidates.
- The identified lead molecule shows potential for further pharmacological investigation due to its favorable binding and non-toxic profile.
- This study highlights the utility of computational methods in accelerating anti-cancer drug discovery.
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