Dimethoxyindoles based thiosemicarbazones as multi-target agents; synthesis, crystal interactions, biological activity and molecular modeling

Yıldız, Minhal; Bingül, Murat; Zorlu, Yunus; Sağlam, Mehmet F.; Boğa, Mehmet; Temel, Mütesir; Koca, Mehmet Serdar; Kandemir, Hakan; Sengul, İbrahim F.

doi:10.1016/j.bioorg.2022.105647

Cited by 26 publications

(12 citation statements)

References 74 publications

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“…The authors have cited additional references within the Supporting Information. [49][50][51][52][53][54][55][56][57][58][59] The Supporting Information includes all experimental details, characterization data of isolated compounds, and chromatograms of the HPLC and GC analyzes.…”

Section: Supporting Information Summarymentioning

confidence: 99%

A Comprehensive Study on a Medicinal and Edible Plant Scorzonera incisa DC., Discussing the Natural Limits of Phytochemical Profiling

Şahin,

Demir,

Boğa

et al. 2023

ChemistrySelect

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Leaves of Scorzonera incisa DC. (Asteraceae) are eaten raw against diabetes and headache. Evaluation of medicinal, edible plants using profiling methods has become a common phenomenon. Petroleum ether (PE), ethyl acetate (EA), and n‐butanol (BU) fractions were prepared from ethanol extract of the aerial parts of the plant. Isolation by HPLC and phenolic profiling by validated LC‐MS/MS method with 53 compounds were conducted on the EA fraction. GC‐MS method was used to profile the PE fraction. In‐vitro inhibitory activities of all fractions against α‐amylase, α‐glucosidase, AChE, BChE, tyrosinase and urease enzymes were measured. Isoorientin, vitexin, cynaroside and chlorogenic acid were isolated and characterized from the EA fraction as major compounds. LC‐MS/MS analysis quantified 36 compounds in the EA fraction. 20 compounds were tentatively determined in the PE fraction. Compounds with the same molecular and fragment ions, a low percentage of identified compounds, and very close polarities were revealed to be some limits of the nature for LC‐MS/MS profiling. Particularly, the presence and amount of substances other than the standard compounds used in the profiling methods and possible misdetections should not be neglected in evaluating medicinal plants and establishing a correlation between compounds and bioactivity.

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Section: Supporting Information Summarymentioning

confidence: 99%

A Comprehensive Study on a Medicinal and Edible Plant Scorzonera incisa DC., Discussing the Natural Limits of Phytochemical Profiling

Şahin,

Demir,

Boğa

et al. 2023

ChemistrySelect

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“…Ligands regulate the lipophilicity, solubility, and binding ability of metal complexes to intracellular targets and play a pivotal role in the anticancer activity of metal compounds . A very interesting class of ligands are thiosemicarbazone compounds that are used as metal chelators and have good antitumor activity. − Among these, several representative compounds, such as triapine, di-2-pyridinone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), and COIT-2, are already in clinical phase I and II studies. − Interestingly, thiosemicarbazones show a multimodal action anticancer mechanism after coordination with metal ions, and this provides a new concept for the development of multimodal action anticancer Pt compounds based on thiosemicarbazones. − …”

Section: Introductionmentioning

confidence: 99%

Human Serum Albumin-Platinum(II) Agent Nanoparticles Inhibit Tumor Growth Through Multimodal Action Against the Tumor Microenvironment

Xu,

Luo,

Zhu

et al. 2023

Mol. Pharmaceutics

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To overcome the limitations of traditional platinum (Pt)-based drugs and further improve the targeting ability and therapeutic efficacy in vivo, we proposed to design a human serum albumin (HSA)-Pt agent complex nanoparticle (NP) for cancer treatment by multimodal action against the tumor microenvironment.We not only synthesized a series of Pt(II) di-2-pyridone thiosemicarbazone compounds and obtained a Pt(II) agent [Pt-(Dp44mT)Cl] with significant anticancer activity but also successfully constructed a novel HSA−Pt(Dp44mT) complex nanoparticle delivery system. The structure of the HSA−Pt(Dp44mT) complex revealed that Pt(Dp44mT)Cl binds to the IIA subdomain of HSA and coordinates with His-242. The HSA-His242-Pt-Dp44mT NPs had an obvious effect on the inhibition of tumor growth, which was superior to that of Dp44mT and Pt(Dp44mT)Cl, and they had almost no toxicity. In addition, the HSA-His242-Pt-Dp44mT NPs were found to kill cancer cells by inducing apoptosis, autophagy, and inhibiting angiogenesis.

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“…Thus, it was possible to compare the activity difference between phenylamine and benzylamine. Thiosemicarbazone structure is a pharmacophore group that is frequently used as both AChE and MAO inhibitors 9‐13 . The thiosemicarbazone group was chosen for this significant activity profile.…”

Section: Introductionmentioning

confidence: 99%

“…Thiosemicarbazone structure is a pharmacophore group that is frequently used as both AChE and MAO inhibitors. [9][10][11][12][13] The thiosemicarbazone group was chosen for this significant activity profile. Aromatic and aliphatic structures that can interact with the peripheral anionic region are preferred for the residue of the thiosemicarbazone part.…”

mentioning

confidence: 99%

“…J = 8.9 Hz), 7.75 (Ar-H, 2H, d, J = 8.9 Hz), 8.05 (-CH=N-, 1H, s),9.91 (-NH, 1H, s), 11.59 (-NH, 1H, s).13 C-NMR (75 MHz, DMSO-d 6 ): m), 7.65 (Ar-H, 2H, d, J = 8.9 Hz), 7.96 (-CH=N-, 1H, s), 8.43 (-NH, 1H, t, J = 5.9 Hz), 11.26 (-NH, 1H, s).13 C-NMR (75 MHz, DMSO-d 6 ): δ = 15.23, 38.63, 47.82, 49.43, 115.18, 115.82 (d, J = 21.8 Hz), 117.97 (d, J = 7.6 Hz), 124.85, 128.93, 142.69, 148.22 (d, J = 1.8 Hz), 152.24, 156.67 (d, J = 235.9 Hz), 176.59 HRMS (m/z): [M + H] + calcd for C 20 H 24 N 5 FS: 386.1809; found 386.1798.…”

mentioning

confidence: 99%

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Synthesis of novel thiosemicarbazone derivatives and investigation of their dual AChE and MAO‐B inhibitor effects

Uytun

Osmaniye

Sağlık

et al. 2022

J of Molecular Recognition

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In this study, 15 thiosemicarbazone derivatives were synthesized. Analysis of the obtained compounds was performed by means of 1H‐NMR, 13C‐NMR and high resolution mass spectroscopy (HRMS) spectroscopic methods. The inhibition effect of the obtained compounds on cholinesterase and monoaminoxidase (MAO) enzymes were investigated with in vitro methods. None of the compounds showed significant activity on the butyrylcholinesterase enzyme. On the other hand, compounds 3b, 3c, 3e, 3k, 3l, 3m, 3n and 3o displayed significant activity on acetylcholinesterase (AChE) while compounds 3f, 3i, 3k, 3l, 3m, 3n, 3o also showed remarkable effects on monoamine oxidase‐B (MAO‐B) enzymes. For the selected compounds, docking studies were performed and the enzyme active site and binding modes were determined. It was revealed that the strongest interaction with AChE and MAO‐B enzyme active sites was observed with the compound 3k. Another important factor in the treatment of diseases affecting the central nervous system such as Alzheimer's is the ability of the compounds to cross the blood‐brain barrier (BBB). Additionally, the agents planned for the treatment of these diseases must also pass the blood‐brain barrier. Therefore, in silico BBB penetration properties of active compounds were investigated.

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Dimethoxyindoles based thiosemicarbazones as multi-target agents; synthesis, crystal interactions, biological activity and molecular modeling

Cited by 26 publications

References 74 publications

A Comprehensive Study on a Medicinal and Edible Plant Scorzonera incisa DC., Discussing the Natural Limits of Phytochemical Profiling

A Comprehensive Study on a Medicinal and Edible Plant Scorzonera incisa DC., Discussing the Natural Limits of Phytochemical Profiling

Human Serum Albumin-Platinum(II) Agent Nanoparticles Inhibit Tumor Growth Through Multimodal Action Against the Tumor Microenvironment

Synthesis of novel thiosemicarbazone derivatives and investigation of their dual AChE and MAO‐B inhibitor effects

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