Bis-indole based triazine derivatives: Synthesis, characterization, in vitro β-glucuronidase anti-cancer and anti-bacterial evaluation along with in silico molecular docking and ADME analysis

Khan, Shoaib; Rehman, Wajid; Hussain, Rafaqat; Obaidullah, Ahmad J.; Alotaibi, Hadil Faris; Alanazi, Mohammed M.; Khan, Muhammad Usman; Khan, Yousaf

doi:10.1016/j.arabjc.2023.104970

Cited by 14 publications

(2 citation statements)

References 39 publications

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“…The PDB files that were created from the MMFF94 have then been used to optimize the molecule geometry of the derivatives of the compounds. To determine the binding locations of the original ligand and its synthesized derivatives, a Lamarckian genetic algorithm was used with a total of 500 runs [31][32][33][34].…”

Section: Docking Studiesmentioning

confidence: 99%

Identification of Indazole-Based Thiadiazole-Bearing Thiazolidinone Hybrid Derivatives: Theoretical and Computational Approaches to Develop Promising Anti-Alzheimer’s Candidates

Khan,

Hussain

et al. 2023

Pharmaceuticals

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A hybrid library of compounds based on indazole-based thiadiazole containing thiazolidinone moieties (1–17) was synthesized. The synthesized compounds were screened in vitro for their inhibition profile against targetedacetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities. All the derivatives demonstrated a varied range of inhibitory activities having IC50 values ranging from 0.86 ± 0.33 μM to 26.73 ± 0.84 μM (AChE) and 0.89 ± 0.12 μM to 27.08 ± 0.19 μM (BuChE), respectively. The results obtained were compared with standard Donepezil drugs (IC50 = 1.26 ± 0.18 μM for AChE) and (1.35 ± 0.37 μM for BuChE), respectively. Specifically, the derivatives 1–17, 1, 9, and 14 were found to be significantly active, with IC50 values of 0.86 ± 0.30, 0.92 ± 0.10, and 1.10 ± 0.37 μM (against AChE) and 0.89 ± 0.12, 0.98 ± 0.48 and 1.19 ± 0.42 μM (against BuChE), respectively.The structure–activity relationship (SAR) studies revealed that derivatives bearing para-CF3, ortho-OH, and para-F substitutions on the phenyl ring attached to the thiadiazole skeleton, as well as meta-Cl, -NO2, and para-chloro substitutions on the phenyl ring, having a significant effect on inhibitory potential. The synthesized scaffolds have been further characterized by using 1H-NMR, 13C-NMR, and (HR-MS) to confirm the precise structures of the synthesized compounds. Additionally, the molecular docking approach was carried out for most active compounds to explore the binding interactions established by most active compounds, with the active sites of targeted enzymes and obtained results supporting the experimental data.

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Section: Docking Studiesmentioning

confidence: 99%

Identification of Indazole-Based Thiadiazole-Bearing Thiazolidinone Hybrid Derivatives: Theoretical and Computational Approaches to Develop Promising Anti-Alzheimer’s Candidates

Khan,

Hussain

et al. 2023

Pharmaceuticals

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“…Alkaloids can be classified in terms of their chemical structure into subclasses such as sterols, pyridoacridines, pyrazinones, pyrroles, isoquinolines, guadinines, aminoimidazoles, indoles, and bis-indoles [ 36 ]. In particular, bis-indolyl alkaloids and their synthetic derivatives, consisting of two indole moieties linked to each other via heterocyclic units or linear chains, are well known because of their broad spectrum of biological properties, including anti-microbial [ 37 , 38 ], anti-viral [ 39 , 40 ], and anti-tumour activities [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ]. Herein, the anticancer activities of Nortopsentins and their derivatives are reviewed.…”

Section: Introductionmentioning

confidence: 99%

Nortopsentins as Leads from Marine Organisms for Anticancer and Anti-Inflammatory Agent Development

Pecoraro,

Terrana,

Panzeca

et al. 2023

Molecules

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The marine environment is an excellent source of molecules that have a wide structural diversity and a variety of biological activities. Many marine natural products (MNPs) have been established as leads for anticancer drug discovery. Most of these compounds are alkaloids, including several chemical subclasses. In this review, we focus on the bis-indolyl alkaloid Nortopsentins and their derivatives with antiproliferative properties. Nortopsentins A–C were found to exhibit in vitro cytotoxicity against the P388 murine leukaemia cell line. Their structural manipulation provided a wide range of derivatives with significant anti-tumour activity against human cell lines derived from different cancer types (bladder, colon, gastric, CNS, liver, lung, breast, melanoma, ovarian, pancreatic, prostate, pleural mesothelioma, renal, sarcoma, and uterus). In vivo assays on animal models also proved that Nortopsentins and related bis-indolyl compounds have potent anti-inflammatory activity. These remarks set the foundation for future investigations into the development of new Nortopsentin derivatives as new anticancer and anti-inflammatory agents.

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Hybrid molecules of thiadiazole-based benzothioate and benzenesulfonothioate: synthesis, structural analysis, and evaluation as potential inhibitors of thymidine phosphorylase and β-glucuronidase through in vitro and in silico approaches

Khan,

Rehman

et al. 2023

Journal of Molecular Structure

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Bis-indole based triazine derivatives: Synthesis, characterization, in vitro β-glucuronidase anti-cancer and anti-bacterial evaluation along with in silico molecular docking and ADME analysis

Cited by 14 publications

References 39 publications

Identification of Indazole-Based Thiadiazole-Bearing Thiazolidinone Hybrid Derivatives: Theoretical and Computational Approaches to Develop Promising Anti-Alzheimer’s Candidates

Identification of Indazole-Based Thiadiazole-Bearing Thiazolidinone Hybrid Derivatives: Theoretical and Computational Approaches to Develop Promising Anti-Alzheimer’s Candidates

Nortopsentins as Leads from Marine Organisms for Anticancer and Anti-Inflammatory Agent Development

Hybrid molecules of thiadiazole-based benzothioate and benzenesulfonothioate: synthesis, structural analysis, and evaluation as potential inhibitors of thymidine phosphorylase and β-glucuronidase through in vitro and in silico approaches

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