Carbohydrate Modifications of Neoandrographolide for Improved Reactive Oxygen Species-Mediated Apoptosis through Mitochondrial Pathway in Colon Cancer

Sharma, Venu; Qayum, Arem; Kaul, Sanjana; Singh, Ajeet; Kapoor, Kamal K.; Mukherjee, Debaraj; Singh, Shashank; Dhar, Manoj K.

doi:10.1021/acsomega.9b01249

Cited by 9 publications

(6 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neoandrographolide directly binds to Rab5 by occupying the GDP/GTP binding channel to inhibit its function, highlighting the great potential of Neoandrographolide as a chemical therapeutic agent for cancer treatment [ 52 ]. Carbohydrate Modifications of Neoandrographolide for Improved Reactive Oxygen Species-Mediated Apoptosis through Mitochondrial Pathway in Colon Cancer [ 53 ]. Little research has been done on Andropanoside, existing studies mainly focus on their chemical structure and their cytotoxic effects toward LNCaP, HepG2, KB, MCF7, and sk-MEL2 human carcinoma cells and NO inhibitory effects in LPS-stimulated RAW264.7 cells [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel natural inhibitors targeting AKT Serine/Threonine Kinase 1 (AKT1) by computational study

et al. 2022

View full text Add to dashboard Cite

Despite great progress, the current cancer treatments often have obvious toxicity and side effects. and a poor prognosis (some patients). One of the reasons for the poor prognosis is that certain enzymes prevent anticancer drugs from killing tumor cells. AKT1 is involved in regulating PI3K/AKT/mTOR, a tumor-generating pathway. Ipatasertib, a highly selective inhibitor of AKT1, is widely used in the treatment of tumors. In this study, many structural and biochemical methodswere used to find better AKT1(Threonine Kinase 1) inhibitors, which laid a foundation for the further development of AKT1 inhibitors and provided new drugs for the treatment of tumors. ZINC15 database and Discovery Studio 4.5, a computer-aided drug screening software with many modules (LibDock for virtual screening, ADME (Absorption, Distribution, Metabolism, Excretion) and TOPKAT (toxicity prediction module) for the toxicity and properties analysis, and MD simulation for stability prediction), were employed. CCK8 assay, ELISA assay genicity and higher tolerance to cytochrome P4502D6. MD simulations indicated they could bind with AKT1 stably in the natural environment. The cell experiment and specific assay for AKT1 inhibition showed they could inhibit the proliferation and AKT1 expression of MG63 cells (Osteosarcoma cells). Moreover, these novel compounds with structural modifications can be potential contributors that lead to further rational drug design for targeting AKT1. Abbreviation AKT1, AKT Serine/Threonine Kinase 1; ADME, absorption, distribution, metabolism, excretion; TOPKAT, toxicity prediction by Computer assisted technology; CCK8, Cell Counting Kit 8; ELISA, Enzyme-linked immunosorbent assay; CYP2D6, cytochrome P4502D6 inhibition; GBM, Glioblastoma; AGC kinase, protein kinase A, G, and C families (PKA, PKC, PKG); PKB, protein kinase B; PAM pathway, PI3K/AKT/mTOR pathway; OS, overall survival; PFS, progression-free survival; LD50, lethal dose half in rats; LOAEL, lowest observed adverse effect level; NPT, normal pressure and temperature; PME, particle mesh Ewald; LINCS, linear constraint solver; RMSD, root-mean-square deviation; BBB, blood–brain barrier; DS, Discovery Studio; DTP, Developmental toxicity potential; PPB, Plasma protein binding; MTD, Maximum Tolerated Dosage; AB, Aerobic Biodegradability; NTP, US. National Toxicology Program; DTP, developmental toxicity potential.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of novel natural inhibitors targeting AKT Serine/Threonine Kinase 1 (AKT1) by computational study

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Lastly, absorbance was recorded at 540 nm in a microplate reader (Tecan Infinite M Nano). IC 50 was determined by GraphPad Prism 6 …”

Section: Methodsmentioning

confidence: 99%

“…IC 50 was determined by GraphPad Prism 6. 55 Reactive Oxygen Species (ROS) Generation Assay. Dye 2′,7″-dichlorofluorescein diacetate (DCFH-DA) was used to measure intracellular ROS production.…”

Section: -Hydroxy-3-methoxy-phenylamine (16b)mentioning

confidence: 99%

1,2,3-Triazole Tethered Hybrid Capsaicinoids as Antiproliferative Agents Active against Lung Cancer Cells (A549)

et al. 2022

View full text Add to dashboard Cite

A series of novel 1,2,3-triazole derivatives of capsaicin and its structural isomer (new natural product hybrid capsaicinoid) were synthesized by exploiting one-/two-point modification of capsaicin without altering the amide linkage (neck). The newly synthesized compounds were screened for their antiproliferative activity against an NCI panel of 60 cancer cell lines at a single dose of 10 μM. Most of the compounds have demonstrated reduced growth between 55 and 95%, whereas capsaicin ( 10 ) has shown reduced growth between 0 and 24%. Compounds showing more than 50% growth inhibition were further evaluated for the IC 50 value. Among the cell lines tested, lung cancer cell lines (A549, NCI-H460) were found to be more susceptible toward most of the synthesized compounds. Compounds 14g and 14j demonstrated good antiproliferative activity in NCI-H460 with IC 50 values of 6.65 and 5.55 μM, respectively, while compounds 18b , 18c , 18f , and 18m demonstrated potential antiproliferative activity in A549 cell lines with IC 50 values ranging between 2.9 and 10.5 μM. Among the compounds, compound 18f was found to demonstrate the best activity with an IC 50 value of 2.91 μM against A549. Furthermore, 18f induces cell cycle arrest at the S-phase and disrupts the mitochondrial membrane potential, reducing cell migration potential by inducing cellular apoptosis and higher ROS generation along with a decrease in mitochondrial membrane potential in addition to surface and nuclear morphological alterations such as a reduction in the number and shrinkage of cells coupled with nuclear blabbing indicating the sign of apoptosis of A549 non-small cell lung cancer cell lines. Compound 18f has emerged as a lead molecule and may serve as a template for further discovery of capsaicinoid scaffolds.

show abstract

“…The plant's aerial parts (leaves and stems) are usually used to extract active substances, which are diterpene lactones, including andrographolide 14‐deoxy‐11,12‐didehydroandrographolide, and neoandrographolide (Neo) 7 . Among these compounds, Neo has been reported to exhibit a broad spectrum of biological activities of anti‐inflammation, anticancer, hypolipidemia 8–10 . However, there is no research data to explore whether Neo is beneficial for MI/R.…”

Section: Introductionmentioning

confidence: 99%

“…7 Among these compounds, Neo has been reported to exhibit a broad spectrum of biological activities of anti-inflammation, anticancer, hypolipidemia. [8][9][10] However, there is no research data to explore whether Neo is beneficial for MI/R. Therefore, the aim of the present study was to evaluate the cardioprotective effect of Neo on MI/R models and investigate its possible mechanism.…”

mentioning

confidence: 97%

Amelioratory effect of neoandrographolide on myocardial ischemic‐reperfusion injury by its anti‐inflammatory and anti‐apoptotic activities

Liu

Zhang

et al. 2021

Environmental Toxicology

View full text Add to dashboard Cite

In the present study, we aimed to evaluate the cardioprotective effect of neoandrographolide (Neo) on myocardial ischemia/reperfusion injury (I/R) models and explore its possible mechanism. We randomly and equally divided male mice into sham-operation, I/R, and I/R + Neo groups. H9C2 cell line and primary neonatal rat cardiomyocytes were induced into the simulated I/R's status and used to further validate the Neo's role in vitro. Heart systolic function, indexes of myocardial injury (IMI), infarct size, pathological change, cell apoptosis, inflammatory cytokines, and indexes related to apoptotic and NF-κB signaling pathways were analyzed in vivo or in vitro after the Neo treatment. Compared to the I/R group, Neo significantly suppressed IMI, infarct size, inflammatory cell infiltration, cell apoptosis, inflammatory cytokines, bax, cleaved caspase-3, P-IKBa, and P-NF-κB protein expressions, and the translocation of NF-kB subunit p65 from the cytoplasm to the nucleus in vivo or in vitro. Still, ejected fraction, fractional shortening, and the bcl-2 protein expression were notably increased after the Neo treatment. Neo could be developed into a new drug for treating myocardial I/R by inhibiting myocardial inflammation and apoptosis, which was closely related to suppressing the activation of bax/bcl-2 and NF-κB signaling pathways.

show abstract

Carbohydrate Modifications of Neoandrographolide for Improved Reactive Oxygen Species-Mediated Apoptosis through Mitochondrial Pathway in Colon Cancer

Cited by 9 publications

References 26 publications

Identification of novel natural inhibitors targeting AKT Serine/Threonine Kinase 1 (AKT1) by computational study

Identification of novel natural inhibitors targeting AKT Serine/Threonine Kinase 1 (AKT1) by computational study

1,2,3-Triazole Tethered Hybrid Capsaicinoids as Antiproliferative Agents Active against Lung Cancer Cells (A549)

Amelioratory effect of neoandrographolide on myocardial ischemic‐reperfusion injury by its anti‐inflammatory and anti‐apoptotic activities

Contact Info

Product

Resources

About