Design and synthesis of 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxyphenyl)-1,3,5-triazin-2-amine analogues as tubulin polymerization inhibitors

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

doi:10.1016/j.bmcl.2017.06.060

Cited by 18 publications

(11 citation statements)

References 44 publications

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“…For HepG2 our inhibitor doses were the same for chlorpromazine, methyl-β-cyclodextrin, cytochalasin D, and genistein. Higher doses of nystatin (200 μg/mL), amiloride (1 mM), and nocodazole (1 mM) were used with the HepG2 cells in accordance with the literature. , Each inhibitor was added to the cells and incubated at 37 °C with 5% CO 2 for 1 h. The inhibitor solution was then removed and replaced with microgels suspended in serum- and phenol-free media. The amount of uptake was measured after 4 h using lysate fluorescence, and our results are reported as a percent control of the untreated sample.…”

Section: Methodsmentioning

confidence: 99%

Mechanosensitive Endocytosis of High-Stiffness, Submicron Microgels in Macrophage and Hepatocarcinoma Cell Lines

Kruger

Givens

Lansakara

et al. 2018

ACS Appl. Bio Mater.

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The mechanical properties of submicron particles offer a unique design space for advanced drug-delivery particle engineering. However, the recognition of this potential is limited by a poor consensus about both the specificity and sensitivity of mechanosensitive endocytosis over a broad particle stiffness range. In this report, our model series of polystyrene-co-poly(N-isopropylacrylamide) (pS-co-NIPAM) microgels have been prepared with a nominally constant monomer composition (50 mol % styrene and 50 mol % NIPAM) with varied bis-acrylamide cross-linking densities to introduce a tuned spectrum of particle mechanics without significant variation in particle size and surface charge. While previous mechanosensitive studies use particles with moduli ranging from 15 kPa to 20 MPa, the pS-co-NIPAM particles have Young’s moduli (E) ranging from 300 to 700 MPa, which is drastically stiffer than these previous studies as well as pure pNIPAM. Despite this elevated stiffness, particle uptake in RAW264.7 murine macrophages displays a clear stiffness dependence, with a significant increase in particle uptake for our softest microgels after a 4 h incubation. Preferential uptake of the softest microgel, pS-co-NIPAM-1 (E = 310 kPa), was similarly observed with nonphagocytic HepG2 hepatoma cells; however, the uptake kinetics were distinct relative to that observed for RAW264.7 cells. Pharmacological inhibitors, used to probe for specific routes of particle internalization, identify actin- and microtubule-dependent pathways in RAW264.7 cells as sensitive particle mechanics. For our pS-co-NIPAM particles at nominally 300–400 nm in size, this microtubule-dependent pathway was interpreted as a phagocytic route. For our high-stiffness microgel series, this study provides evidence of cell-specific, mechanosensitive endocytosis in a distinctly new stiffness regime that will further broaden the functional landscape of mechanics as a design space for particle engineering.

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Section: Methodsmentioning

confidence: 99%

Mechanosensitive Endocytosis of High-Stiffness, Submicron Microgels in Macrophage and Hepatocarcinoma Cell Lines

Kruger

Givens

Lansakara

et al. 2018

ACS Appl. Bio Mater.

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“…Narva et al . in 2017, synthesised 4‐morpholino‐6‐(1,2,3,6‐tetrahydropyridin‐4‐yl)‐ N ‐(3,4,5‐trimethoxyphenyl)‐1,3,5‐triazin‐2‐amine derivatives ( 32 – 33 ) and evaluated them for tubulin polymerization inhibition [51] . The synthesized derivatives were examined for their anti‐proliferative activity against four cancer cell lines HeLa, HepG2 (Human hepatic cell line), A549 (adenocarcinomic human alveolar basal epithelial cells) and MCF‐7.…”

Section: Pharmacologymentioning

confidence: 99%

Recent Advances on the s‐Triazine Scaffold with Emphasis on Synthesis, Structure‐Activity and Pharmacological Aspects: A Concise Review

et al. 2021

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Triazine nuclei have occupied a propitious place in pharmaceutical chemistry due to their diverse biological behaviour. The marketed drugs such as Azacitidine, Melarsoprol, Altretamine and Almitrine display broad pharmacological activities like anti‐cancer, anti‐parasitic, anti‐inflammatory, Respiratory stimulant and many more. Literature studies reveal that the 2, 4, and 6 substitution on s‐triazine is important for varied biological activities. This diversity in pharmacological activities of triazine scaffold has fascinated the various researchers to further investigate its applications in the treatment of several diseases. This review is complementary to earlier reports and aims to review the work reported on various synthetic methods and biological activities of substituted s‐triazine derivatives from 2016 to 2020 with a list of patents. The enriched structure‐activity relationship may open the doors for further rational drug development of s‐triazine containing analogues as good clinical candidates.

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“…Thus, 1,3,5-triazine-2-carbohydrazides exhibited Rad6B inhibitory activity, 9 while macrocyclic pyrazolo [1,5-a] [1,3,5]triazines showed potent inhibition of CK2 protein kinase. 10 Other mechanisms of action are related to the inhibition of phosphatidylinositol 3-kinase a/mammalian target of rapamycin (PI3Ka/mTOR), 11 carbonic anhydrase (CA), [12][13][14] human topoisomerase IIa, 15 dihydrofolate reductase (hDHFR) 16 and tubulin polymerization 17 (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, biological evaluation, and in silico studies of novel chalcone- and pyrazoline-based 1,3,5-triazines as potential anticancer agents

et al. 2020

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Design and synthesis of 4-morpholino-6-(1,2,3,6-tetrahydropyridin-4-yl)-N-(3,4,5-trimethoxyphenyl)-1,3,5-triazin-2-amine analogues as tubulin polymerization inhibitors

Cited by 18 publications

References 44 publications

Mechanosensitive Endocytosis of High-Stiffness, Submicron Microgels in Macrophage and Hepatocarcinoma Cell Lines

Mechanosensitive Endocytosis of High-Stiffness, Submicron Microgels in Macrophage and Hepatocarcinoma Cell Lines

Recent Advances on the s‐Triazine Scaffold with Emphasis on Synthesis, Structure‐Activity and Pharmacological Aspects: A Concise Review

Synthesis, biological evaluation, and in silico studies of novel chalcone- and pyrazoline-based 1,3,5-triazines as potential anticancer agents

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