Molecular insights of hyaluronic acid - ethambutol and hyaluronic acid - isoniazid drug conjugates act as promising novel drugs for the treatment of tuberculosis

The present study examines cellular targeted drug delivery (CTDD) pattern of two novel Hyaluronic acid (HA) Tuberculosis Drug (TB) conjugates and its efficacy and strong binding affinity towards TB molecular protein targets. Two TB drugs ethambutol (EB) and isoniazid (IN) and their Hyaluronic acid c...

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Published in:Journal of biomolecular structure & dynamics 2023-05, Vol.41 (8), p.3562-3573
Main Authors: Thirumalaisamy, R., Aroulmoji, V., Iqbal, Muhammad Nasir, Saride, Shreyas, Bhuvaneswari, M., Deepa, M., Sivasankar, C., Khan, Riaz
Format: Article
Language:English
Subjects:
Antitubercular Agents - chemistry
ethambutol
Ethambutol - pharmacology
Ethambutol - therapeutic use
Humans
Hyaluronic Acid
isoniazid
Isoniazid - pharmacology
Life Sciences
Molecular Docking Simulation
molecular modeling
Mycobacterium tuberculosis
Mycobacterium tuberculosis - metabolism
Pharmaceutical Preparations
Pharmaceutical sciences
Tuberculosis - drug therapy
Tuberculosis - microbiology
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Summary:The present study examines cellular targeted drug delivery (CTDD) pattern of two novel Hyaluronic acid (HA) Tuberculosis Drug (TB) conjugates and its efficacy and strong binding affinity towards TB molecular protein targets. Two TB drugs ethambutol (EB) and isoniazid (IN) and their Hyaluronic acid conjugates (HA-EB & HA-IN) were tested for its metabolism, toxicity and excretion prediction through In silico tools they revealed hyaluronic acid conjugate of two TB drugs exhibited good drug profile over their free form of TB drugs. Further these four molecules subjected to In silico molecular docking study with four potential Mycobacterium tuberculosis target proteins (3PD8, 4Y0L, 5DZK and 6GAU). Molecular docking study revealed that hyaluronic conjugates (HA-EB & HA-IN) exhibit significant binding affinity and excellent docking scores with all screened molecular protein targets of TB over their free form of drug. Further molecular dynamic simulation was calculated for the four drug molecules (EB, IN, HA- EB & HA-IN) with DNA gyrase enzyme (PDB ID 6GAU) of Mycobacterium tuberculosis and the MDS results revealed that both the conjugates with the TB target protein possessed good number of interaction with binding pocket residues and good simulation scores than the free form of drugs. Communicated by Ramaswamy H. Sarma
ISSN:0739-1102
1538-0254
DOI:10.1080/07391102.2022.2051748