Dual or multi-targeting inhibitors: The next generation anticancer agents

Raghavendra, Narasimha; Pingili, Divya; Kadasi, Sundeep; Mettu, Akhila; Prasad, Senthamizh

doi:10.1016/j.ejmech.2017.10.021

Cited by 227 publications

(115 citation statements)

References 189 publications

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“…In an effort towards new drug design and development, the improvement of molecules by the combination of diverse pharmacophores could lead to compounds with interesting biological profiles sulfonamide is one such pharmacophore to hybridize with heterocyclic units . Few recent examples of such hybrid clinical agents derived with sulfonamide unit are depicted in Figure .…”

Section: Introductionmentioning

confidence: 62%

Anticancer Potential of N‐Sulfonyl Noscapinoids: Synthesis and Evaluation

et al. 2020

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Noscapine is an alkaloid with a basic phthalideisoquinoline moiety and is well recognized as an antitussive drug. It is obtained from opium poppy Papaver somniferum and demonstrates a rather safe toxicity profile in vitro. Recent studies found noscapine and its analogues to have anticancer activity against mammalian cancer cell lines by modulating microtubule assembly. In the present study, we report the synthesis and evaluation of cytotoxicity of a series of N‐sulfonyl noscapinoids 6 a–n obtained by reaction of nornoscapine with various aryl/heteroaryl sulfonyl chlorides. To assess the antiproliferative activity of the novel derivatives 6 a–n, SRB assay was performed in four different human cancer cell lines, MIAPaCa‐2 (pancreatic), HeLa (cervical), SK−N−SH (neuroblastoma) and DU145 (prostate cancer). The study identified four compounds 6 e–g and 6 j ability to arrest cell‐cycle at the G2/M phase and cytotoxic potential against the human pancreatic cancer cell line MIAPaCa‐2. We observed that these compounds 6 e–g and 6 j induce microtubule depolymerisation and cause cell cycle arrest at the G2/M phase thereby resulting in caspase‐3 and PARP activation leading to cell death. In silico molecular docking studies of these compounds showed non‐covalent interactions like Van der Waals and hydrogen‐bonding with tubulin protein and with good binding energy.

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Section: Introductionmentioning

confidence: 62%

Anticancer Potential of N‐Sulfonyl Noscapinoids: Synthesis and Evaluation

et al. 2020

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“…Through the topological indexes analysis, a total of 32 nodes that were screened as the most important targets genes contribute to the colon cancer treatment of ginger. Among these genes, proto-oncogene tyrosine-protein kinase (SRC), with the maximum interacting edges, is a family of non-receptor tyrosine kinases that plays an essential role in the selection and maturation of developing T-cells in the thymus and in the function of mature T-cells [24]. A previous study reported that SRC is a potential oncogene, which contributes to colon cancer cell proliferation through FRα/c-SRC/ERK1/2/NFκB/TP53 pathway [25].…”

Section: Discussionmentioning

confidence: 99%

Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking

Zhang¹,

Wang²,

Liu³

et al. 2020

Preprint

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Background: Colon cancer is increasing recently but the high cost and adverse side effects experienced always leads to treatment drop out. Zingiber officinale, commonly known as ginger, is a popular herbal medicine and this study was aimed to identify the active compounds from ginger and to investigate its anti-cancer mechanisms through network pharmacology construction. Results: Ginger compounds were discerned through the TCMSP, which were filtered by the metrics of oral bioavailability and drug likeness, and its related targets were searched. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. Six potential active compounds, 288 interacting targets in addition to 1356 disease-related targets were collected, of which 114 intersection targets were obtained. The PPI network showed that 32 targets including SRC, PIK3R1, and TP53 were identified as key targets. These targets were mainly associated with the biological processes like transmembrane receptor protein tyrosine kinase signaling pathway, regulation of cellular protein localization, cellular response to oxidative stress. KEGG enrichment manifested that ginger probably produced preventive effects against colon cancer by regulating significant signaling pathway like pathway in cancer, hepatitis B, and estrogen signaling pathway. TP53, HSP90AA1, MAPK8, JAK2, CASP3, and ERBB2 could be viewed as the most potential target proteins, which were validated by molecular docking simulation.Conclusion: This study demonstrated the multi-component, multi-target, and multi-pathway characteristics of ginger, providing novel insight for ginger compounds developed as new drug for anti-colon cancer.

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“…Nowadays, it is gaining a great importance in anticancer drug discovery. In this field, a promising computational approach for identification of target combinations, and virtual screening for the design of multi-targeting ligands include data mining, ligand and structure-based analyses [70]. Design I-Kappa-B KinaseB (IKK-B) inhibitor, is another example of design a small molecule using a computational approach which is a key player in the NF-B signaling pathway, represents yet another potential target for the treatment of cancer in addition to inflammation [71].…”

Section: Application Of Computational Methods For Anticancer Drugmentioning

confidence: 99%

Drug Discovery - Yesterday and Tomorrow: The Common Approaches in Drug Design and Cancer

On¹

2018

CCLSJ

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The process of drug discovery has undergone radical changes and development over years. Traditionally, the drugs were discovered by employing chemistry and pharmacology-based cautious approach. When natural products were the most important source of drugs or drug precursors, but the conventional randomized drug research phenomenon was no longer effective at that time due to many negatives of these approaches like: high expenses of discovering new drugs, time-consuming and reduced success guarantee. Thus, with the development of the era, the concept of "Rational Drug Design" has enabled drug target identification and validation to be more specific. In addition, several novel technologies and approaches have been introducing economics, proteomics and other omics areas such as 3D QSAR, pharmacophore modeling and other, which playing a promising role in accelerating the pace of drug discovery process. Their view of the current research focuses on the importance of drug discovery in modern times and shows how old methods have been replaced and summarized. Some of examples of molecules are identified in addition to computational approaches used to discover it, specifically in the field of anticancer drug design

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Dual or multi-targeting inhibitors: The next generation anticancer agents

Cited by 227 publications

References 189 publications

Anticancer Potential of N‐Sulfonyl Noscapinoids: Synthesis and Evaluation

Anticancer Potential of N‐Sulfonyl Noscapinoids: Synthesis and Evaluation

Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking

Drug Discovery - Yesterday and Tomorrow: The Common Approaches in Drug Design and Cancer

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