Synthesis and biological evaluation of pyrrolo[2,3- b ]pyridine analogues as antiproliferative agents and their interaction with calf thymus DNA

Suresh, N.; Chitti, Surendar; Bala, Bhaskara Rao; Alvala, Mallika; Jain, Nishant; Kondapalli, Venkata Gowri Chandra Sekhar

doi:10.1016/j.ejmech.2016.02.059

Cited by 43 publications

(23 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DNA is viewed as one of the main molecular targets for toxic effect of many alkaloids. Generally speaking, the interaction between DNA and drugs was investigated with Calf thymus DNA (CT-DNA) in vitro 15 , 16 ; while little attention is focused on whether drug could really bind or cleave DNA in vivo . Thus, DNA-adducts need to be examined using UV-Visible spectroscopy after exposure to various concentrations of DDAs.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of Aconitum alkaloid and its interaction with calf thymus DNA by multi-spectroscopic techniques

Liu

Tan

Han

et al. 2017

Sci Rep

View full text Add to dashboard Cite

The cytotoxicities of three aconitum alkaloids- aconitine, hypaconitine and mesaconitine, and their abilities to bind DNA have been explored. Rat myocardial cells H9c2 were treated with aconitum alkaloids and assessed the cytotoxicities by using MTT assay and flow cytometry. Apoptosis was evidenced by the results of the annexin V/propidium iodide (PI) assay. Aconitine was found to be the most toxic in rat myocardial cells H9c2 in three aconitum alkaloids. At the same time, DNA adducts were isolated and then analyzed by UV-Vis spectroscopy after exposure to alkaloids, which indicated that three alkaloids could bind to DNA in rat myocardial cells H9c2. Furthermore, their binding modes were investigated by UV-Visible, fluorescence, DNA melting studies and ionic strength effect. Results indicated that the interaction between three alkaloids and DNA were intercalation coupled with electrostatic effect. The estimated binding constants were between 4.83 × 105 M−1 to 9.85 × 105 M−1 for three alkaloids at 298 K.

show abstract

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of Aconitum alkaloid and its interaction with calf thymus DNA by multi-spectroscopic techniques

Liu

Tan

Han

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…In 2016, Narva and co-workers [ 41 ] synthetized new pyrrolo[2,3- b ]pyridines to evaluate their antitumor activity against the three human cancer cell lines A549, HeLa, and MDA-MB-231. Among all, compounds 17a - k showed their maximum growth inhibitory effect at concentrations from 0.17 to 25.9 μM).…”

Section: Anticancer Activitymentioning

confidence: 99%

Bioactive pyrrole-based compounds with target selectivity

Petri

Spanò

Spatola

et al. 2020

European Journal of Medicinal Chemistry

163

View full text Add to dashboard Cite

The discovery of novel synthetic compounds with drug-like properties is an ongoing challenge in medicinal chemistry. Natural products have inspired the synthesis of compounds for pharmaceutical application, most of which are based on N -heterocyclic motifs. Among these, the pyrrole ring is one of the most explored heterocycles in drug discovery programs for several therapeutic areas, confirmed by the high number of pyrrole-based drugs reaching the market. In the present review, we focused on pyrrole and its hetero-fused derivatives with anticancer, antimicrobial, and antiviral activities, reported in the literature between 2015 and 2019, for which a specific target was identified, being responsible for their biological activity. It emerges that the powerful pharmaceutical and pharmacological features provided by the pyrrole nucleus as pharmacophore unit of many drugs are still recognized by medicinal chemists.

show abstract

“…Cells were stained with the WST-1 cell proliferation reagent instead of sulforhodamine B in some experiments and absorbance were measured at 440 nm. The three dose response parameters GI 50 , TGI and LC 50 were calculated for each experimental compound as follows [ 48 ]: Where Ti is the absorbance of the solubilized Sulforhodamine B (SRB) (representing the number of cells) of the five different concentrations of the compound used in the test, Tz is the absorbance of the SRB at time zero, and C is the absorbance of the SRB of the control growth.…”

Section: Methodsmentioning

confidence: 99%

Novel Anthra[1,2-c][1,2,5]Thiadiazole-6,11-Diones as Promising Anticancer Lead Compounds: Biological Evaluation, Characterization & Molecular Targets Determination

et al. 2016

View full text Add to dashboard Cite

The novel compounds NSC745885 and NSC757963 developed at our laboratory were tested against a panel of 60 cancer cell lines at the National Cancer Institute, USA, and a panel of 39 cancer cell lines at the Japanese Foundation of Cancer Research. Both compounds demonstrated selective unique multi-log differential patterns of activity, with GI50 values in the sub-micro molar range against cancer cells rather than normal cardiac cells. NSC757963 showed high selectivity towards the leukemia subpanel. Activities of both compounds strongly correlated to expression of NFKB1 and CSNK2B genes, implying that they may inhibit the NF-κB pathway. Immunocytochemical microscopy of OVCAR-3 cells showed clear cytosolic accumulation of the NF-κB p65 subunit following treatment. Western blotting showed dose dependent inhibition of the nuclear expression of the NF-κB p65 subunit with subsequent accumulation in the cytosol following treatment. Docking experiments showed binding of both compounds to the NF-κB activator IKKβ subunit preventing its translocation to the nucleus. Collectively, these results confirm the ability of our compounds to inhibit the constitutively active NF-κB pathway of OVCAR-3 cells. Furthermore, COMPARE analysis indicated that the activity of NSC757963 is similar to the antituberculosis agent rifamycin SV, this was confirmed by testing the antimycobacterial activity of NSC757963 against Mycobacterium tuberculosis, results revealed potent activity suitable for use in clinical practice. Molecular properties and Lipinski’s parameters predicted acceptable bioavailability properties with no indication of mutagenicity, tumorigenicity, irritability and reproductive effects. Oral absorption experiments using the human Caco-2 model showed high intestinal absorption of NSC745885 by passive transport mechanism with no intestinal efflux or active transport mechanisms. The unique molecular characterization as well as the illustrated anticancer spectra of activity and bioavailability properties warrant further development of our compounds and present a foundation brick in the pre-clinical investigations to implement such compounds in clinical practice.

show abstract

Synthesis and biological evaluation of pyrrolo[2,3- b ]pyridine analogues as antiproliferative agents and their interaction with calf thymus DNA

Cited by 43 publications

References 53 publications

Cytotoxicity of Aconitum alkaloid and its interaction with calf thymus DNA by multi-spectroscopic techniques

Cytotoxicity of Aconitum alkaloid and its interaction with calf thymus DNA by multi-spectroscopic techniques

Bioactive pyrrole-based compounds with target selectivity

Novel Anthra[1,2-c][1,2,5]Thiadiazole-6,11-Diones as Promising Anticancer Lead Compounds: Biological Evaluation, Characterization & Molecular Targets Determination

Contact Info

Product

Resources

About