Design, synthesis and biological evaluation of novel indole-xanthendione hybrids as selective estrogen receptor modulators

Singla, Ramit; Gupta, Kunj Bihari; Upadhyay, Shishir; Dhiman, Monisha; Jaitak, Vikas

doi:10.1016/j.bmc.2017.11.040

Cited by 24 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Singla et al [36], synthesized indole-xanthendione analogs and screened their anticancer potential and estrogen receptor alpha binding affinity utilizing ER α responsive T47D breast cancer cell line. Compounds 36 and 37 displayed most promising anticancer potential targeting on ER- α (Table 12, Fig.…”

Section: Introductionmentioning

confidence: 99%

Estrogen alpha receptor antagonists for the treatment of breast cancer: a review

Sharma

Kumar

2018

Chemistry Central Journal

View full text Add to dashboard Cite

BackgroundCancer is at present one of the leading causes of death in the world. It accounts for 13% of deaths occurred worldwide and is continuously rising, with an estimated million of deaths up to 2030. Due to poor availability of prevention, diagnosis and treatment of breast cancer, the rate of mortality is at alarming level globally. In women, hormone-dependent estrogen receptor positive (ER+) breast cancer making up approximately 75% of all breast cancers. Hence, it has drawn the extensive attention of researchers towards the development of effective drugs for the treatment of hormone-dependent breast cancer. Estrogen, a female sex hormone has a vital role in the initiation and progression of breast malignancy. Therefore, estrogen receptor is the central target for the treatment of breast cancer.ConclusionIn this review, we have studied various classes of antiestrogens that have been designed and synthesized with selective binding for estrogen alpha receptor (ER). Since estrogen receptor α is mainly responsible for the breast cancer initiation and progression, therefore there is need of promising strategies for the design and synthesis of new therapeutic ligands which selectively bind to estrogen alpha receptor and inhibit estrogen dependent proliferative activity.

show abstract

Section: Introductionmentioning

confidence: 99%

Estrogen alpha receptor antagonists for the treatment of breast cancer: a review

Sharma

Kumar

2018

Chemistry Central Journal

View full text Add to dashboard Cite

show abstract

“…Jaitak and their group [90] reported SERMs (selective estrogen receptor modulators) based on xanthendione scaffolds in the same year. Compound 51 exhibited IC 50 value of 17.94 � 1.0 μM and 16.55 � 1.95 nM against T47D an ER-� binding affinity respectively.…”

Section: Chemmedchemmentioning

confidence: 99%

Contribution of Knoevenagel Condensation Products toward the Development of Anticancer Agents: An Updated Review

2022

View full text Add to dashboard Cite

Knoevenagel condensation is an entrenched, prevailing, prominent arsenal following greener principles in the generation of α, β-unsaturated ketones/carboxylic acids by involving carbonyl functionalities and active methylenes. This reaction has proved to be a major driving force in many multicomponent reactions indicating the prolific utility toward the development of biologically fascinating molecules. This eminent reaction was acclimatised on different pharmacophoric aldehydes (benzimidazole, β-carboline, phenanthrene, indole, imidazothiadiazole, pyrazole etc.) and active methylenes (oxindole, barbituric acid, Meldrum's acid, thiazolidinedione etc.) to generate the library of chemical compounds. Their potential was also explicit to understand the significance of functionalities involved, which thereby evoke further developments in drug discovery. Furthermore, most of these reaction products exhibited remarkable anticancer activity in nanomolar to micromolar ranges by targeting different cancer targets like DNA, microtubules, Topo-I/II, and kinases (PIM, PARP, NMP, p300/CBP) etc. This review underscores the efficiency of the Knoevenagel condensation explored in the past six-year to generate molecules of pharmacological interest, predominantly toward cancer. The present review also provides the aspects of structure-activity relationships, mode of action and docking study with possible interaction with the target protein.

show abstract

“…It bears a dibenzo‐γ‐pyrone skeleton ( Figure 1) [3] and multiple substitution sites which can form diverse structures and exhibit various biological activities, such as antitumor, antibacterial, antioxidative, antiinflammation and neuroprotective effects, etc [4–8] . Especially, the excellent antitumor activity of xanthone has attracted numerous researchers to extract or synthesize xanthones for the development of prospective antitumor drug candidates [9–12] . Xanthone could exert excellent antitumor effect through a variety of action mechanisms and one of important biological targets was DNA [13] .…”

Section: Introductionmentioning

confidence: 99%

Effect of Bis‐Dimethylamine Substitution on DNA Binding Property and Cytotoxic Activity of Polyhydroxyxanthone

Shen

Kou

Chen

et al. 2022

Chemistry & Biodiversity

View full text Add to dashboard Cite

A bis-dimethylamine substituted xanthone (Xan-2) was obtained by cationic modification of the free C3 and C6 hydroxy groups of 1,3,6-trihydroxyxanthone (Xan-1) which was isolated from Polygala hongkongensis Hemsl.. The results of the spectroscopic analysis, melting profiles, electrophoretic migration, PCR assay and molecular docking indicated that the hydrophobic plane of Xan-1 and Xan-2 could intercalate into the DNA base pairs meanwhile the basic amine alkyl chain of Xan-2 could bind with DNA phosphate framework via electrostatic interaction. Thus, Xan-2 exhibited higher DNA binding affinity than Xan-1. Further study showed that Xan-2 could inhibit the proliferation of HeLa, SGC-7901 and A549 cells effectively by MTT assay and induce apoptosis of HeLa cells as detected by AO/EB staining and flow cytometry assay. Interestingly, Xan-2 exhibited selective cytotoxicity to cells, which was proved by its relatively low inhibitory effect on Raw 264.7 cell. What these studies mean is that disubstituted amine alkyl chains will play an important role in DNA binding property and cytotoxic activity, providing a direction for the development of novel potential antitumor agents.

show abstract

Design, synthesis and biological evaluation of novel indole-xanthendione hybrids as selective estrogen receptor modulators

Cited by 24 publications

References 30 publications

Estrogen alpha receptor antagonists for the treatment of breast cancer: a review

Estrogen alpha receptor antagonists for the treatment of breast cancer: a review

Contribution of Knoevenagel Condensation Products toward the Development of Anticancer Agents: An Updated Review

Effect of Bis‐Dimethylamine Substitution on DNA Binding Property and Cytotoxic Activity of Polyhydroxyxanthone

Contact Info

Product

Resources

About