Novel 3-chloro-6-nitro-1H-indazole derivatives as promising antileishmanial candidates: synthesis, biological activity, and molecular modelling studies
Аутори
Mokhtar Mohamed Abdelahi, MohamedEl Bakri, Youness
Lai, Chin-Hung
Subramani, Karthikeyan
Anouar, El Hassane
Ahmad, Sajjad
Benchidmi, Mohammed
Mague, Joel T.
Popović-Djordjević, Jelena
Goumri-Said, Souraya
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
An efficient pathway was disclosed for the synthesis of 3-chloro-6-nitro-1H-indazole derivatives by 1,3-dipolar cycloaddition on dipolarophile compounds 2 and 3. Faced the problem of separation of two regioisomers, a click chemistry method has allowed us to obtain regioisomers of triazole-1,4 with good yields from 82 to 90% were employed. Also, the antileishmanial biological potency of the compounds was achieved using an MTT assay that reported compound 13 as a promising growth inhibitor of Leishmania major. Molecular docking demonstrated highly stable binding with the Leishmania trypanothione reductase enzyme and produced a network of hydrophobic and hydrophilic interactions. Molecular dynamics simulations were performed for TryR-13 complex to understand its structural and intermolecular affinity stability in a biological environment. The studied complex remained in good equilibrium with a structure deviation of ∼1–3 Å. MM/GBSA binding free energies illustrated the high stability of T...ryR-13 complex. The studied compounds are promising leads for structural optimisation to enhance the antileishmanial activity.
Кључне речи:
1,2,3-Triazole / antileishmanial activity / isooxazoline / isoxazole / molecular dynamicsИзвор:
Journal of Enzyme Inhibition and Medicinal Chemistry, 2022, 37, 1, 151-167Издавач:
- Taylor and Francis Ltd.
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200026 (Универзитет у Београду, Институт за хемију, технологију и металургију - ИХТМ) (RS-MESTD-inst-2020-200026)
DOI: 10.1080/14756366.2021.1995380
ISSN: 1475-6366
WoS: 000729294900001
Scopus: 2-s2.0-85121289833
Институција/група
Poljoprivredni fakultetTY - JOUR AU - Mokhtar Mohamed Abdelahi, Mohamed AU - El Bakri, Youness AU - Lai, Chin-Hung AU - Subramani, Karthikeyan AU - Anouar, El Hassane AU - Ahmad, Sajjad AU - Benchidmi, Mohammed AU - Mague, Joel T. AU - Popović-Djordjević, Jelena AU - Goumri-Said, Souraya PY - 2022 UR - http://aspace.agrif.bg.ac.rs/handle/123456789/6001 AB - An efficient pathway was disclosed for the synthesis of 3-chloro-6-nitro-1H-indazole derivatives by 1,3-dipolar cycloaddition on dipolarophile compounds 2 and 3. Faced the problem of separation of two regioisomers, a click chemistry method has allowed us to obtain regioisomers of triazole-1,4 with good yields from 82 to 90% were employed. Also, the antileishmanial biological potency of the compounds was achieved using an MTT assay that reported compound 13 as a promising growth inhibitor of Leishmania major. Molecular docking demonstrated highly stable binding with the Leishmania trypanothione reductase enzyme and produced a network of hydrophobic and hydrophilic interactions. Molecular dynamics simulations were performed for TryR-13 complex to understand its structural and intermolecular affinity stability in a biological environment. The studied complex remained in good equilibrium with a structure deviation of ∼1–3 Å. MM/GBSA binding free energies illustrated the high stability of TryR-13 complex. The studied compounds are promising leads for structural optimisation to enhance the antileishmanial activity. PB - Taylor and Francis Ltd. T2 - Journal of Enzyme Inhibition and Medicinal Chemistry T1 - Novel 3-chloro-6-nitro-1H-indazole derivatives as promising antileishmanial candidates: synthesis, biological activity, and molecular modelling studies EP - 167 IS - 1 SP - 151 VL - 37 DO - 10.1080/14756366.2021.1995380 ER -
@article{ author = "Mokhtar Mohamed Abdelahi, Mohamed and El Bakri, Youness and Lai, Chin-Hung and Subramani, Karthikeyan and Anouar, El Hassane and Ahmad, Sajjad and Benchidmi, Mohammed and Mague, Joel T. and Popović-Djordjević, Jelena and Goumri-Said, Souraya", year = "2022", abstract = "An efficient pathway was disclosed for the synthesis of 3-chloro-6-nitro-1H-indazole derivatives by 1,3-dipolar cycloaddition on dipolarophile compounds 2 and 3. Faced the problem of separation of two regioisomers, a click chemistry method has allowed us to obtain regioisomers of triazole-1,4 with good yields from 82 to 90% were employed. Also, the antileishmanial biological potency of the compounds was achieved using an MTT assay that reported compound 13 as a promising growth inhibitor of Leishmania major. Molecular docking demonstrated highly stable binding with the Leishmania trypanothione reductase enzyme and produced a network of hydrophobic and hydrophilic interactions. Molecular dynamics simulations were performed for TryR-13 complex to understand its structural and intermolecular affinity stability in a biological environment. The studied complex remained in good equilibrium with a structure deviation of ∼1–3 Å. MM/GBSA binding free energies illustrated the high stability of TryR-13 complex. The studied compounds are promising leads for structural optimisation to enhance the antileishmanial activity.", publisher = "Taylor and Francis Ltd.", journal = "Journal of Enzyme Inhibition and Medicinal Chemistry", title = "Novel 3-chloro-6-nitro-1H-indazole derivatives as promising antileishmanial candidates: synthesis, biological activity, and molecular modelling studies", pages = "167-151", number = "1", volume = "37", doi = "10.1080/14756366.2021.1995380" }
Mokhtar Mohamed Abdelahi, M., El Bakri, Y., Lai, C., Subramani, K., Anouar, E. H., Ahmad, S., Benchidmi, M., Mague, J. T., Popović-Djordjević, J.,& Goumri-Said, S.. (2022). Novel 3-chloro-6-nitro-1H-indazole derivatives as promising antileishmanial candidates: synthesis, biological activity, and molecular modelling studies. in Journal of Enzyme Inhibition and Medicinal Chemistry Taylor and Francis Ltd.., 37(1), 151-167. https://doi.org/10.1080/14756366.2021.1995380
Mokhtar Mohamed Abdelahi M, El Bakri Y, Lai C, Subramani K, Anouar EH, Ahmad S, Benchidmi M, Mague JT, Popović-Djordjević J, Goumri-Said S. Novel 3-chloro-6-nitro-1H-indazole derivatives as promising antileishmanial candidates: synthesis, biological activity, and molecular modelling studies. in Journal of Enzyme Inhibition and Medicinal Chemistry. 2022;37(1):151-167. doi:10.1080/14756366.2021.1995380 .
Mokhtar Mohamed Abdelahi, Mohamed, El Bakri, Youness, Lai, Chin-Hung, Subramani, Karthikeyan, Anouar, El Hassane, Ahmad, Sajjad, Benchidmi, Mohammed, Mague, Joel T., Popović-Djordjević, Jelena, Goumri-Said, Souraya, "Novel 3-chloro-6-nitro-1H-indazole derivatives as promising antileishmanial candidates: synthesis, biological activity, and molecular modelling studies" in Journal of Enzyme Inhibition and Medicinal Chemistry, 37, no. 1 (2022):151-167, https://doi.org/10.1080/14756366.2021.1995380 . .