Synthesis and photobiological applications of naphthalimide–benzothiazole conjugates: cytotoxicity and topoisomerase IIα inhibition

Singh, Iqubal; Luxami, Vijay; Choudhury, Diptiman; Paul, Kamaldeep

doi:10.1039/d1ra04148g

Cited by 11 publications

(6 citation statements)

References 60 publications

(107 reference statements)

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“…The binding of amsacrine to topo IIα is similar to that of etoposide based on the interacting amino acid residues, thus only compounds 58a, 58c, 58f, and 58i showed similar binding, which could be used to infer their anticancer properties. Similar results had been reported for the docking interaction of human topoisomerase IIα (PDB: 1ZXM) with naphthalimide-benzothiazole conjugates and etoposide, which indicated amino acid residues Val57, Gln59, Gln60, Met61, Trp62, Tyr72, Phe77, Pro79, Tyr82, Lys83, Lys306, Gln309, Ile311, Phe313, Ala318, Ser320, Lys321 and Glu379 [29].…”

Section: Discussionsupporting

confidence: 85%

Synthesis, SAR, and in Silico ADME Screening Studies of Some 9-Amino-3-Phenylacridone Derivatives as Topoisomerase II Inhibitors

Oyedele,

Fatoki,

Dalvie

et al. 2023

OJMC

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Cancer is a leading cause of death globally, claiming about 9.6 million lives and approximately 420 million new cases of cancer will be diagnosed in the world by the year 2025. The aim of this study was to synthesize and computationally evaluate pharmacological potential of some derivatives of 9-amino-3phenylacridone, as topoisomerase II (Topo II) inhibitors. In this study, 10 derivatives of 3-phenyl-9-aminoacridone were chemically synthesized and characterized, and the potential pharmacological indications of these compounds were computationally predicted by methods such as ADMET prediction, molecular target prediction and molecular docking. The results showed that two derivatives (58e and 58j) were non-permeant of blood-brain barrier, and this property was found similar to that of amsacrine and etoposide. The results of molecular docking of the ten derivatives of 3-phenyl-9-aminoacridone that were synthesized in this work showed that the synthetic compounds (58a-j) and the standard drugs have overall best binding affinities for human acetylcholine esterase than butyrylcholinesterase, and overall best binding affinities for human topo IIα than human topo IIβ. Overall, the results of this study suggest that the synthetic compounds 58a, 58c, 58f, 58g, and 58i could probably inhibit topo IIα by catalytic inhibition as seen with amsacrine, but only 58b and 58e possessed DNA non-intercalation properties as seen with etoposide, serving as topo II poison. In conclusion, this study showed that 3-phenyl-9-aminoacridone derivatives are potential inhibitor of topo IIα/β both by catalytic inhibition and poison as non-intercalator of DNA.

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Section: Discussionsupporting

confidence: 85%

Synthesis, SAR, and in Silico ADME Screening Studies of Some 9-Amino-3-Phenylacridone Derivatives as Topoisomerase II Inhibitors

Oyedele,

Fatoki,

Dalvie

et al. 2023

OJMC

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“…Singh et al [88] have reported napthalimide-benzothiazole conjugates as cytotoxic agents. Compounds 37 and 38 (Figure 25)…”

Section: Phosphatidylinositol-3-kinases (Pi3k)/akt Inhibitorsmentioning

confidence: 99%

“…Singh et al [ 88 ] have reported napthalimide‐benzothiazole conjugates as potent cytotoxic agents. Compounds 37 and 38 (Figure 25) were found to be the most potent in the series, exhibiting excellent inhibitory activity with IC 50 values of 0.14 and 0.31 µM against A549 and 3.81 and 3.49 µM against MCF‐7 cancer cell lines, respectively.…”

Section: Benzothiazole Scaffold‐based Enzyme Inhibitorsmentioning

confidence: 99%

Benzothiazole‐based apoptosis inducers: A comprehensive overview and future prospective

Kamboj,

Mahore,

Husain

et al. 2024

Archiv der Pharmazie

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Cancer has become a major concern in healthcare globally, and over time, incidences and prevalence of cancer are increasing. To counter this, a lot of anticancer drugs are approved and are in clinical use, playing a pivotal role in its treatment. Due to drug resistance and adverse effects, a continuous demand for novel, potent, and safe candidates to treat cancer is always there. Over the last few decades, various heterocyclic ring‐based derivatives have been explored and reported in the literature. In this regard, benzothiazole scaffold‐based compound emerged as the versatile ring for developing novel and safe anticancer candidates. In this article, we have reported various benzothiazole heterocyclic ring‐based derivatives demonstrating potent antiproliferative activity by induction of apoptosis via an intrinsic pathway in a dose‐dependent manner. These compounds also displayed inhibition of different enzymes, for example, Aurora kinase, epidermal growth factor receptor, vascular endothelial growth factor receptor, phosphoinositide kinases, DNA topoisomerase, and tubulin polymerases. This study focused on a comprehensive overview of antiproliferative activity, structure–activity relationship, apoptosis induction activity, and enzyme inhibition by benzothiazole‐based compounds.

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“…Benzothiazole-indole-naphthalimide hybrid 37 (IC 50 : 0.38 µM) with low toxic effects (IC 50 : >10 µM) in normal HEK293 cells was comparable to etoposide (IC 50 : 0.33 µM) against MCF-7 cells. [70] The SAR indicated that the naphthalimide moiety and the allyl group at the N-1 position of naphthalimide moiety were vital for the high activity. [70,71] Mechanistically, hybrid 37 might suppress topoisomerase IIα to produce its antiproliferative properties.…”

Section: Indole/isatin-azole Hybridsmentioning

confidence: 99%

“…[70] The SAR indicated that the naphthalimide moiety and the allyl group at the N-1 position of naphthalimide moiety were vital for the high activity. [70,71] Mechanistically, hybrid 37 might suppress topoisomerase IIα to produce its antiproliferative properties. Isatin-1,3,4-thiadiazole hybrid 38 (GI 50 : 0.71-1.98 µM) revealed strong broad-spectrum efficacy against a panel of MCF-7, HS 578 T, BT549, T47D, MDA-MB-231, and MDA-MB-468 BC cell lines, [72] whereas hybrids 39a-c (IC 50 : 9.0 µM) were comparable to doxorubicin (IC 50 : 4.8 µM) against MCF-7 cancer cells.…”

Section: Indole/isatin-azole Hybridsmentioning

confidence: 99%

The anti‐breast cancer potential of indole/isatin hybrids

Wang,

Huang,

Yuan

et al. 2023

Archiv der Pharmazie

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Breast cancer (BC) is one of the most prevalent malignancies and the major contributor to cancer mortality in women globally, with a high degree of heterogeneity and a dismal prognosis. As drug resistance is responsible for most BC fatalities and advanced BC is currently considered incurable, finding innovative anti‐BC chemotherapeutics is urgently required. Indole and its analog isatin (indole‐1H‐2,3‐dione) are prominent pharmacophores in the development of novel medications, and their derivatives exhibit strong anticancer activities, also against BC. In particular, indole/isatin hybrids exhibit significant potency against BC including multidrug‐resistant forms and excellent selectivity by influencing a variety of biological targets associated with the disease, supplying helpful building blocks for the identification of potential new BC treatment options. This review includes articles from 2020 to the present and provides insights into the in vitro and in vivo anti‐BC potential, molecular mechanisms, and structure–activity relationships (SARs) of indole/isatin hybrids that may be helpful in the development of innovative anti‐BC chemotherapeutics.

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Synthesis and photobiological applications of naphthalimide–benzothiazole conjugates: cytotoxicity and topoisomerase IIα inhibition

Abstract: Conjugates of naphthalimide, benzothiazole, and indole moieties are synthesized that show excellent cytotoxicity against A549 (lung), MCF7 (breast), and HeLa (cervix) cancer cell lines with IC50 values in the range of 0.14–8.59 μM.

Cited by 11 publications

References 60 publications

Synthesis, SAR, and in Silico ADME Screening Studies of Some 9-Amino-3-Phenylacridone Derivatives as Topoisomerase II Inhibitors

Synthesis, SAR, and in Silico ADME Screening Studies of Some 9-Amino-3-Phenylacridone Derivatives as Topoisomerase II Inhibitors

Benzothiazole‐based apoptosis inducers: A comprehensive overview and future prospective

The anti‐breast cancer potential of indole/isatin hybrids

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