scholarly journals Synthetic Integrin-Targeting Dextran-Fc Hybrids Efficiently Inhibit Tumor Proliferation In Vitro

2021 ◽  
Vol 9 ◽  
Author(s):  
Hendrik Schneider ◽  
Simon Englert ◽  
Arturo Macarrón Palacios ◽  
Jorge Alberto Lerma Romero ◽  
Ataurehman Ali ◽  
...  
Keyword(s):  
Click Reaction ◽  
Biological Evaluation ◽  
Rgd Peptides ◽  
Design Synthesis ◽  
Antitumor Potential ◽  
Molecular Hybrids ◽  
The Stability ◽  
Proliferation In Vitro ◽  
Synthesis And Biological Evaluation

Herein, we present the design, synthesis, and biological evaluation of novel integrin-targeting molecular hybrids combining RGD peptides and a potent cytotoxin presented on dextran polysaccharides. Based on an aglycosylated Fc as a centerpiece, endosomal-cleavable cytotoxic agent monomethyl auristatin E (MMAE) and dextran as multimerization site were covalently connected by two bioorthogonal enzyme-mediated reactions site-specifically. Decoration of dextran with cyclic RGD peptides, introduced by copper “click” reaction, resulted in the final constructs with the potential to kill integrin-overexpressing tumor cells. We found that these modifications had little impact on the stability of the Fc scaffold and the RGD-bearing construct showed good binding properties of αvβ3-expressing U87MG cells. Furthermore, the construct showed a remarkable antiproliferative activity. These results demonstrate the general capability of our design to provoke receptor-mediated endocytosis upon binding to the cellular surface, followed by endosomal cleavage of the linkage between Fc-dextran and MMAE and its subsequent release. Our approach opens new avenues to transcribe small molecule binders into tailor-made multimeric molecular hybrids with antitumor potential.

scholarly journals Design, Synthesis and Biological Evaluation of Novel 1, 3, 4-Oxadiazole Bearing Pyridine Moiety

2019 ◽  
pp. 300-307
Author(s):  
Asma D. Ambekari ◽  
Shrinivas K. Mohite
Keyword(s):  
Antimicrobial Activity ◽  
Mass Spectra ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Pyridine Moiety ◽  
Anti Inflammatory ◽  
Physicochemical Data ◽  
Synthesis And Biological Evaluation

Series of novel substituted Synthesis of N-{[5-(substituted)-1,3,4-oxadiazole-2-yl] carbamothioyl} derivatives containing 1,3,4-oxadiazole moiety were synthesized by microwave as a green chemistry method and conventional method by using pyridine 3- carboxylic acid as a starting material. The structures of the synthesized compounds were characterized by physicochemical data, IR, Mass spectra and 1HNMR. All the newly synthesized compound screened for their antimicrobial and In-vivo and In-vitro Anti-inflammatory studies. Anti-inflammatory studies revealed that compound 4f showed significant in-vivo and in-vitro anti-inflammatory activity as well potent antimicrobial activity.

Design, synthesis, and biological evaluation of new series of 2-amido-1,3,4-thiadiazole derivatives as cytotoxic agents

2016 ◽  
Vol 71 (3) ◽  
pp. 205-210 ◽  
Author(s):  
Ali Almasirad ◽  
Loghman Firoozpour ◽  
Maliheh Nejati ◽  
Najmeh Edraki ◽  
Omidreza Firuzi ◽  
...  
Keyword(s):  
Human Tumor ◽  
Inhibitory Effect ◽  
Biological Evaluation ◽  
Cytotoxic Agents ◽  
Antitumor Activities ◽  
Design Synthesis ◽  
Ethidium Bromide Staining ◽  
Thiadiazole Derivatives ◽  
Synthesis And Biological Evaluation

AbstractA series of novel 1,3,4-thiadiazole derivatives bearing an amide moiety were designed, synthesized, and evaluated for their in vitro antitumor activities against HL-60, SKOV-3 and MOLT-4 human tumor cell lines by MTT assay. Ethyl 2-((5-(4-methoxybenzamido)-1,3,4-thiadiazol-2-yl)thio)acetate (5f) showed the best inhibitory effect against SKOV-3 cells, with an IC50 value of 19.5 μm. In addition, the acridine orange/ethidium bromide staining assay in SKOV-3 cells suggested that the cytotoxic activity of 5f occurs via apoptosis.

scholarly journals Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259008
Author(s):  
Leandro da Costa Clementino ◽  
Guilherme Felipe Santos Fernandes ◽  
Igor Muccilo Prokopczyk ◽  
Wilquer Castro Laurindo ◽  
Danyelle Toyama ◽  
...  
Keyword(s):  
Parasite Burden ◽  
Peritoneal Macrophages ◽  
Biological Evaluation ◽  
Antileishmanial Activity ◽  
Dual Effect ◽  
Design Synthesis ◽  
Murine Peritoneal Macrophages ◽  
Synthesis And Biological Evaluation

Leishmaniasis is a neglected disease that affects 12 million people living mainly in developing countries. Herein, 24 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antileishmanial activity. Compound 4f, a furoxan derivative, was particularly remarkable in this regard, with EC50 value of 3.6 μM against L. infantum amastigote forms and CC50 value superior to 500 μM against murine peritoneal macrophages. In vitro studies suggested that 4f may act by a dual effect, by releasing nitric oxide after biotransformation and by inhibiting cysteine protease CPB (IC50: 4.5 μM). In vivo studies using an acute model of infection showed that compound 4f at 7.7 mg/Kg reduced ~90% of parasite burden in the liver and spleen of L. infantum-infected BALB/c mice. Altogether, these outcomes highlight furoxan 4f as a promising compound for further evaluation as an antileishmanial agent.

Design, synthesis, and biological evaluation of glycine-based molecular tongs as inhibitors of Aβ1–40 aggregation in vitro

2008 ◽  
Vol 16 (9) ◽  
pp. 4810-4822 ◽  
Author(s):  
Saverio Cellamare ◽  
Angela Stefanachi ◽  
Diana A. Stolfa ◽  
Teodora Basile ◽  
Marco Catto ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Design Synthesis ◽  
Synthesis And Biological Evaluation

Design, synthesis and biological evaluation of (1,3-diphenyl-1H-pyrazol-4-yl) methyl benzoate derivatives as potential BRAFV600E inhibitors

RSC Advances ◽  
2014 ◽  
Vol 4 (95) ◽  
pp. 52702-52711 ◽  
Author(s):  
Ya-Juan Qin ◽  
Man Xing ◽  
Ya-Liang Zhang ◽  
Jigar A. Makawana ◽  
Ai-Qin Jiang ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Biological Evaluation ◽  
Methyl Benzoate ◽  
Design Synthesis ◽  
Synthesis And Biological Evaluation ◽  
Potent Inhibitory Activity ◽  
Benzoate Derivatives

A series of (1,3-diphenyl-1H-pyrazol-4-yl) methyl benzoate derivatives (6a–10d) were designed and synthesized and evaluated as BRAFV600 inhibitors. Among them, compound 10a showed the most potent inhibitory activity against A375, WM266.4 and BRAFV600Ein vitro with IC50 values of 1.36 μM, 0.94 μM and 0.11 μM, respectively.

Design, synthesis and biological evaluation of C(6)-indole celastrol derivatives as potential antitumor agents

RSC Advances ◽  
2015 ◽  
Vol 5 (25) ◽  
pp. 19620-19623 ◽  
Author(s):  
Kaiyong Tang ◽  
Jinwen Huang ◽  
Junfang Pan ◽  
Xuan Zhang ◽  
Wei Lu
Keyword(s):  
Cancer Cells ◽  
Antitumor Agents ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
New Class ◽  
Synthesis And Biological Evaluation ◽  
Antiproliferative Activities ◽  
Potential Antitumor

A new class of C(6)-indole substituted celastrol derivatives were designed and synthesized. Among all these synthesized molecules, compound 4f and 4h displayed excellent in vitro antiproliferative activities against Bel7402 cancer cells.

scholarly journals Design, Synthesis, and Biological Evaluation of Aromatic Amide-Substituted Benzimidazole-Derived Chalcones. The Effect of Upregulating TP53 Protein Expression

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1162
Author(s):  
Lintao Wu ◽  
Yuting Yang ◽  
Zhijun Wang ◽  
Xi Wu ◽  
Feng Su ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Human Cancer ◽  
Biological Evaluation ◽  
Mechanistic Study ◽  
Design Synthesis ◽  
Human Cancer Cell Lines ◽  
Aromatic Amide ◽  
Synthesis And Biological Evaluation ◽  
Tp53 Protein

A series of benzimidazole-derived chalcones containing aromatic amide substituent were designed and synthesized. All of the chalcone compounds were tested for their in vitro antitumor activity against human cancer cell lines (HCT116, HepG2, A549, and CRL-5908). The antiproliferative activity of compounds 3, 6, 9, 14, 15, 16 against HCT116 cells was significantly better than that that of 5-Fluorouracil (IC50: 94.63 µM). The antitumor activity of these compounds showed obvious differences between the wild type HCT116 and mutant HCT116 (TP53−/−) cells. A preliminary mechanistic study suggested that these compounds act by upregulating the expression of TP53 protein in tumor cells without inhibiting the MDM2-TP53 interaction.

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