Design and synthesis of a new class of cryptophycins based tubulin inhibitors

Kumar, Arvind; Kumar, Manjeet; Sharma, Sunny; Guru, Santosh Kumar; Bhushan, Shashi; Shah, Bhahwal Ali

doi:10.1016/j.ejmech.2014.11.068

Cited by 13 publications

(7 citation statements)

References 42 publications

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“…MTT assay was performed to assess the antiproliferative activities of compounds 27 , 28 . Cells were treated with compounds at various concentrations for 24 h or 48 h. 20 µL of freshly prepared MTT reagent was added to cells and incubated at 37 °C for 2 h. The supernatant growth medium was removed and replaced with DMSO (100 µL) to dissolve the formazan crystals.…”

Section: Methodsmentioning

confidence: 99%

“…Three individual experiments were performed and results were expressed as percent inhibitions at various doses of each compound. IC 50 means the concentration of the compound, which inhibits 50% of cell growth 28 .…”

Section: Methodsmentioning

confidence: 99%

“…Cancer cells (1 × 10 6 /ml) were treated with different concentrations of compound (5 and10 µM) for 24 h, fixed in cold 70% alcohol in PBS, washed, digested with DNase free RNase (400 µg/mL) at 37 °C for 45 min and stained with propidium iodide (10 µg/ml). Cells were analyzed for PI-DNA fluorescence by flow cytometerically using FACS CALIBUR (Becton Dickinson, Franklin Lakes, New Jersey, USA) 28 – 30 . The fluorescence intensity of subG0/GI cell fraction represents the dead cell population.…”

Section: Methodsmentioning

confidence: 99%

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Synthesis of Saccharumoside-B analogue with potential of antiproliferative and pro-apoptotic activities

Rayavarapu

Yarla

Kadiri

et al. 2017

Sci Rep

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A new series of phenolic glycoside esters, saccharumoside-B and its analogs (9b-9n, 10) have been synthesized by the Koenigs-Knorr reaction. Antiproliferative activities of the compounds (9b-9n, 10) were evaluated on various cancer cell lines including, MCF-7 breast, HL-60 leukemia, MIA PaCa-2 pancreatic, DU145 prostate, HeLa cervical and CaCo-2 colon, as well as normal human MCF10A mammary epithelial and human peripheral blood mononuclear cells (PBMC) by MTT assay. Compounds (9b-9n, 10) exhibited considerable antiproliferative effects against cancer cells with IC50 range of 4.43 ± 0.35 to 49.63 ± 3.59 µM, but they are less cytotoxic on normal cells (IC50 > 100 µM). Among all the compounds, 9f showed substantial antiproliferative activity against MCF-7 and HL-60 cells with IC50 of 6.13 ± 0.64 and 4.43 ± 0.35, respectively. Further mechanistic studies of 9f were carried out on MCF-7 and HL-60 cell lines. 9f caused arrest of cell cycle of MCF-7 and HL-60 cells at G0/G1 phase. Apoptotic population elevation, mitochondrial membrane potential loss, increase of cytosolic cytochrome c and Bax levels, decrease of Bcl-2 levels and enhanced caspases-9 and -3 activities were observed in 9f-treated MCF-7 and HL-60 cells. These results demonstrate anticancer and apoptosis-inducing potentials of 9f in MCF-7 and HL-60 cells via intrinsic pathway.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Synthesis of Saccharumoside-B analogue with potential of antiproliferative and pro-apoptotic activities

Rayavarapu

Yarla

Kadiri

et al. 2017

Sci Rep

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“…The transition state with anti –Re face 17 was predicted to be most stable. The method was also extended for the synthesis of cryptophycins based macrocyclic depsipeptides 18 , α,β‐unsaturated δ‐lactones 19 and iso‐chromenones in high enantioselectivities. In particular, cryptophycins are naturally occurring macrocyclic depsipeptides which are considered to be the most potent compounds known in tubulin dynamics with excellent activity against multidrug‐resistant cancer cell lines.…”

Section: C–c Bond Cleavage Of Styrenesmentioning

confidence: 99%

Carbon‐Carbon and Carbon‐Heteroatom Bond Formation Reactions Using Unsaturated Carbon Compounds

Sultan

Shah

2018

The Chemical Record

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The carbon-carbon and carbon-heteroatom bond formation reactions are considered as a fundamental tool in synthetic organic chemistry. They have been effectively utilized in the synthesis of medicinally significant molecules, agrochemicals and valuable compounds in material sciences. This has been primarily enabled by highly efficient protocols arising from divergent mechanistic pathways. In this personal account, we aim to discuss some recent advances in carbon-carbon or carbon-heteroatom bond formation reactions to which our group has actively contributed. More specifically, this record focuses on the use of unsaturated carbon compounds for the construction of CÀC and CÀX bonds. . Cu(OTf ) 2 catalyzed oxidative amidation of terminal alkynes. Scheme 3. Oxidative amidation diketonization of styrenes. Scheme 6. Access to substituted quinolines from styrenes. Scheme 7. Vinyl acetate mediated cross-aldol reactions.

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“…Truncated cryptophycins have also been studied based on cryptophycin‐24 (arenastatin A), as a parent compound . These modifications led to a dramatically reduced cytotoxicity (Figure ).…”

Section: Cryptophycin Analogs and Sar Studiesmentioning

confidence: 99%

Cryptophycins: cytotoxic cyclodepsipeptides with potential for tumor targeting

Weiß

Figueras

Borbély

et al. 2017

Journal of Peptide Science

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Cryptophycins are a class of 16-membered highly cytotoxic macrocyclic depsipeptides isolated from cyanobacteria. The biological activity is based on their ability to interact with tubulin. They interfere with microtubule dynamics and prevent microtubules from forming correct mitotic spindles, which causes cell-cycle arrest and apoptosis. Their strong antiproliferative activities with 100-fold to 1000-fold potency compared with those of paclitaxel and vinblastine have been observed. Cryptophycins are highly promising drug candidates, as their biological activity is not negatively affected by P-glycoprotein, a drug efflux system commonly found in multidrug-resistant cancer cell lines and solid tumors. Cryptophycin-52 had been investigated in phase II clinical trials but failed because of its high neurotoxicity. Recently, cryptophycin conjugates with peptides and antibodies have been developed for targeted delivery in tumor therapy.

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Design and synthesis of a new class of cryptophycins based tubulin inhibitors

Cited by 13 publications

References 42 publications

Synthesis of Saccharumoside-B analogue with potential of antiproliferative and pro-apoptotic activities

Synthesis of Saccharumoside-B analogue with potential of antiproliferative and pro-apoptotic activities

Carbon‐Carbon and Carbon‐Heteroatom Bond Formation Reactions Using Unsaturated Carbon Compounds

Cryptophycins: cytotoxic cyclodepsipeptides with potential for tumor targeting

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