Synthesis of indolo/pyrroloazepinone-oxindoles as potential cytotoxic, DNA-intercalating and Topo I inhibitors

Kadagathur, Manasa; Shaikh, Arbaz Sujat; Panda, Biswabandan; George, Joel; Phanindranath, Regur; Sigalapalli, Dilep Kumar; Bhale, Nagesh A.; Godugu, Chandraiah; Nagesh, Narayana; Shankaraiah, Nagula; Tangellamudi, Neelima D.

doi:10.1016/j.bioorg.2022.105706

Cited by 12 publications

(7 citation statements)

References 66 publications

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“…Additionally, it keeps track of the cells that have kept their ability to form colonies after being exposed to agents that cause cell death (chemotherapeutic agents or radiations). 49 Compound 13c ’s effective and broad-spectrum proliferative inhibition in this work motivated us to investigate how it affected NCI-H460 cells’ ability to form cell colonies (one of the most sensitive cell lines as determined in previous NCI assays). Ten days following the compound 13c treatment, colony development was assessed.…”

Section: Resultsmentioning

confidence: 99%

“…The comprehensive procedures of biological assays of the target sulphonamides series I ( 3a–c, 5a–d , and 7a–e ) and series II ( 9, 11a,b, 13a–e, and 15a,b ) are presented in the Supplementary materials , including; CA I, II, IX, and XII inhibition studies, 33 NCI-USA screening, 50 , 72 antiproliferative activities under hypoxic conditions, 73 toxicity towards normal human cells, 47 cell migration study, 48 colony formation assay, 49 apoptosis assay, 74 and cell cycle analysis. 75 , 76 …”

Section: Experimental Protocolsmentioning

confidence: 99%

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Dependence on linkers’ flexibility designed for benzenesulfonamides targeting discovery of novel hCA IX inhibitors as potent anticancer agents

Tawfik

Belal

Abourehab

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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Herein we reported the design and synthesis of two series comprising twenty-two benzenesulfonamides that integrate the s -triazine moiety. Target compounds successfully suppressed the hCA IX, with IC 50 ranging from 28.6 to 871 nM. Compounds 5d , 11b , 5b , and 7b were the most active analogues, which inhibited hCA IX isoform in the low nanomolar range ( K I = 28.6, 31.9, 33.4, and 36.6 nM, respectively). Furthermore, they were assessed for their cytotoxic activity against a panel of 60 cancer cell lines following US-NCI protocol. According to five-dose assay, 13c showed significant anticancer activity than 5c with GI 50 -MID values of 25.08 and 189.01 µM, respectively. Additionally, 13c ’s effects on wound healing, cell cycle disruption, and apoptosis induction in NCI-H460 cancer cells were examined. Further, docking studies combined with molecular dynamic simulation showed a stable complex with high binding affinity of 5d to hCA IX, exploiting a favourable H-bond and lipophilic interactions. HIGHLIGHTS Carbonic anhydrase (CA) inhibitors comprising rigid and flexible linkers were developed. Compound 5d is the most potent CA IX inhibitor in the study (IC50: 28.6 nM). Compounds 5c and 13c displayed the greatest antiproliferative activity towards 60 cell lines. Compound 13c exposed constructive outcomes on normal cell lines, metastasis, and wound healing. Molecular docking and molecular dynamics (MDs) simulation was utilised to study binding mode.

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Section: Resultsmentioning

confidence: 99%

Section: Experimental Protocolsmentioning

confidence: 99%

Dependence on linkers’ flexibility designed for benzenesulfonamides targeting discovery of novel hCA IX inhibitors as potent anticancer agents

Tawfik

Belal

Abourehab

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Indoloazepinone-isatin hybrids 74a,b (IC 50 : 10.55 and 17.38 µM) were more active than 5-fluorouracil (IC 50 : 24.78 µM) against MCF-7 cells and merited further investigations. [114] Indolo [1,2- was comparable to that of doxorubicin (IC 50 : 0.66 and 0.45 µM). [115,116] Mechanistically, indolo[1,2-a]quinoxaline 75 potentially suppressed sirtuin type 1 (SIRT1) to produce its antiproliferative effect.…”

Section: Miscellaneous Indole/isatin Hybridsmentioning

confidence: 99%

“…Indoloazepinone‐isatin hybrids 74a,b (IC 50 : 10.55 and 17.38 µM) were more active than 5‐fluorouracil (IC 50 : 24.78 µM) against MCF‐7 cells and merited further investigations. [ 114 ]…”

Section: Miscellaneous Indole/isatin 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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“…[ 1,2 ] Cancer cells were known to alter their flux autonomously by involving different metabolic pathways, which leads to an increase in the demand of oxidative stress which is required for the initiation and progression of tumor. [ 3 ] Globally, cancer accounts for the major cause of death after cardiovascular complications. The World Health Organization (WHO) reported approximately 10 million deaths in 2020 due to different types of cancer, and 14 million new cases of cancer are reported, which is estimated to reach 30 million by the end of 2024.…”

Section: Introductionmentioning

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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Synthesis of indolo/pyrroloazepinone-oxindoles as potential cytotoxic, DNA-intercalating and Topo I inhibitors

Cited by 12 publications

References 66 publications

Dependence on linkers’ flexibility designed for benzenesulfonamides targeting discovery of novel hCA IX inhibitors as potent anticancer agents

Dependence on linkers’ flexibility designed for benzenesulfonamides targeting discovery of novel hCA IX inhibitors as potent anticancer agents

The anti‐breast cancer potential of indole/isatin hybrids

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

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