One-pot synthesis of some new regioselective 4β-pyrazolepodophyllotoxins as DNA topoisomerase-II targeting anticancer agents

Nagavath, Rajkumar; Nukala, Satheesh Kumar; Narsimha, Sirassu; Sagam, Ravikumar Reddy; Manchal, Ravinder; Suresh, Palaniswamy; Thirukovela, Narasimha Swamy

doi:10.1016/j.molstruc.2021.131724

Cited by 12 publications

(6 citation statements)

References 34 publications

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“…Nagavath et al synthesized novel 4β-aryl pyrazole-epipodophyllotoxin derivatives as topoisomerase II inhibitors [ 88 ]. Compounds 64 and 65 exhibited superior anticancer activity versus the standard drug against five cancer cell lines with IC 50 values ranging from 1 to 100 nM.…”

Section: Inhibitors Of Other Targetsmentioning

confidence: 99%

Recent Advances in the Development of Pyrazole Derivatives as Anticancer Agents

Zhang

et al. 2023

IJMS

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Pyrazole derivatives, as a class of heterocyclic compounds, possess unique chemical structures that confer them with a broad spectrum of pharmacological activities. They have been extensively explored for designing potent and selective anticancer agents. In recent years, numerous pyrazole derivatives have been synthesized and evaluated for their anticancer potential against various cancer cell lines. Structure–activity relationship studies have shown that appropriate substitution on different positions of the pyrazole ring can significantly enhance anticancer efficacy and tumor selectivity. It is noteworthy that many pyrazole derivatives have demonstrated multiple mechanisms of anticancer action by interacting with various targets including tubulin, EGFR, CDK, BTK, and DNA. Therefore, this review summarizes the current understanding on the structural features of pyrazole derivatives and their structure-activity relationships with different targets, aiming to facilitate the development of potential pyrazole-based anticancer drugs. We focus on the latest research advances in anticancer activities of pyrazole compounds reported from 2018 to present.

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Section: Inhibitors Of Other Targetsmentioning

confidence: 99%

Recent Advances in the Development of Pyrazole Derivatives as Anticancer Agents

Zhang

et al. 2023

IJMS

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“…It was found that C4‐N‐substituted podophyllotoxin derivatives have also shown superior anticancer activity via DNA topoisomerase II inhibition [15] . Previously, we have synthesized C4‐podophyllotoxin derivatives as DNA topoisomerase‐II targeting anticancer agents [9f,16] . Accordingly, the molecular docking studies of three active compounds ( 6 e , 6 j and 6 o ) were carried out by taking DNA topoisomerase II (PDB ID‐ 3QX3) as the target protein, which was downloaded as pdb file from protein data bank and the results are shown in table s1, ESI [17] .…”

Section: Chemistrymentioning

confidence: 99%

Anticancer Evaluation of Some New 4β‐Imidazolopodophyllotoxin ‐Aromatic Amides

Nagavath¹,

Nukala²,

Sagam³

et al. 2022

ChemistrySelect

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Herein, we described the synthesis of some new aromatic amides of 4β‐imidazolopodophyllotoxin (6 a–p) and their anticancer evaluation against four human cancer cell lines like MCF‐7 (breast), A549 (lung), Hela (cervical) and DU‐145 (prostate). Out of all, compounds 6 d, 6 e, 6 g, 6 i, 6 j, 6 l, 6 n and 6 o were found to be active with IC50 values in the range of 0.59‐10 μM. Specifically, compound 6 o showed greater potency against all the cell lines than the standard etoposide. Predominantly, compounds 6 e, 6 j and 6 o observed to be 3 to 4 times more potent against DU‐145 than the standard. The molecular docking studies of three active compounds 6 e, 6 j and 6 o on target protein DNA topoisomerase II were also conducted and found that binding affinity and free energies obtained were in good covenant with the corresponding IC50 values. Finally, the results of in silico ADMET revealed that, compounds 6 e, 6 j and 6 o have shown 100 % intestinal absorption and none of them exhibited AMES and hepato toxicity.

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“…Hence, in continuation of our work on developing some new biologically significant heterocycles [26a–n] and by keeping in mind the above mentioned medicinal applications of CA‐4, thiazolidine‐2,4‐dione and 1,2,3‐triazole we have designed the compounds (Figure 1) consisting of the three pharmacophores by taking the advantages of the pharmacophore hybridization approach [27,28] …”

Section: Introductionmentioning

confidence: 99%

Ring‐B Modification of Combretastatin A‐4 to Generate Thiazolidine‐2,4‐dione‐1,2,3‐triazole Hybrids as Tubulin Polymerization Inhibitors

Vanaparthy,

Bokkala,

Thirukovela

et al. 2023

ChemistrySelect

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In this work we have described the synthesis of thiazolidine‐2,4‐dione‐1,2,3‐triazole hybrids (7 a–n) via ring‐B modification of Combretastatin A‐4 involving reactions namely Knoevenagel condensation, O‐propargylation and finally copper (I) catalyzed azide‐alkyne cycloaddition (CuAAC). They were tested for the in vitro anticancer activity against A549, MCF‐7 and HeLa cell lines using MTT assay where some compounds were exhibited more potency than the Nocodazole. In vitro tubulin polymerization inhibition assay for the same compounds revealed that they were more potent in inhibiting tubulin with IC50 values ranging from 0.22 μM to 0.64 μM compared reference drug Combretastatin A‐4. Molecular docking studies of active compounds with α,β‐tubulin revealed that they compounds have more binding energies than that of combretastatin A‐4. Finally, in silico pharmacokinetic profile was achieved for the same compounds using SWISS/ADME and pkCSM, where some of them have followed Lipinski rule and Veber rule.

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One-pot synthesis of some new regioselective 4β-pyrazolepodophyllotoxins as DNA topoisomerase-II targeting anticancer agents

Cited by 12 publications

References 34 publications

Recent Advances in the Development of Pyrazole Derivatives as Anticancer Agents

Recent Advances in the Development of Pyrazole Derivatives as Anticancer Agents

Anticancer Evaluation of Some New 4β‐Imidazolopodophyllotoxin ‐Aromatic Amides

Ring‐B Modification of Combretastatin A‐4 to Generate Thiazolidine‐2,4‐dione‐1,2,3‐triazole Hybrids as Tubulin Polymerization Inhibitors

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