Design, synthesis, and anticancer activity of phosphonic acid diphosphate derivative of adenine-containing butenolide and its water-soluble derivatives of paclitaxel with high antitumor activity

One of the promising methods of creating antitumor drugs is the screening of potential antitumor agents among synthesized compounds. Nitrogen-based heterocycle analogues are an extremely important class of organic substances that are widely used in medical chemistry. [1,2,4]Triazolo[3,4-b][1,3,4] thiadiazoles are among the little-studied and hard-to-reach members of this class of compounds. The aim of our work was to synthesize some new 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, as well as the study of their antitumor activity. The objects of study were 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. The composition and structure of the synthesized compounds were confirmed by the data of elemental analysis and 1H NMR spectroscopy. The antitumor activity of the synthesized compounds was studied in the framework of the international scientific program of the National Cancer Institute (Bethesda, Maryland, USA) DTP NCI (Developmental Therapeutic Program). The synthesis of 11 derivatives of 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles was carried out. These substances are obtained by the interaction of 5-arylfuran-2-carboxylic acids with 5-substituted 4-amino-4H-1,2,4-triazolo-3-thiols. Primary screening revealed individual 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles, which showed pronounced selective antitumor activity. The most active among the tested compounds were 3 d, 3 e and 3 j, which were further investigated during secondary screening. The results of these studies confirm the high antitumor activity of these compounds. The proposed approaches and the developed synthesis protocols made it possible to obtain a series of new 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. The results of studies of the antitumor activity of the synthesized compounds made it possible to single out 3 highly active compounds with high antitumor activity, which gives reason to consider this condensed system as a promising molecular framework for the design of potential antitumor agents.

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Design, Synthesis, and Anticancer Activity of New Derivatives of Thiazole and Imidazole

Russian Journal of General Chemistry ◽

10.1134/s1070363220120191 ◽

2020 ◽

Vol 90 (12) ◽

pp. 2350-2355

Author(s):

I. M. El-Deen ◽

E. H. Elsayed ◽

M. El-Ahwany ◽

M. S. Abd El-Azez

Keyword(s):

Anticancer Activity ◽

Design Synthesis ◽

Derivatives Of

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Enhance of Tumor Targeting by Receptor-Mediated Endocytosis Using Low Molecular Water-Soluble Chitosan Nanoparticles Loaded with Anticancer Agent

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.342-343.469 ◽

2007 ◽

Vol 342-343 ◽

pp. 469-472 ◽

Cited By ~ 2

Author(s):

Dong Gon Kim ◽

Min Ja Jang ◽

Chang Yong Choi ◽

Tae Hyeong Kim ◽

Mi Kyeong Jang ◽

...

Keyword(s):

Antitumor Activity ◽

Anticancer Agent ◽

Drug Carrier ◽

Chitosan Nanoparticles ◽

Water Soluble ◽

Molecular Water ◽

Low Molecular Weight ◽

Receptor Mediated Endocytosis ◽

Chitosan Nanoparticle ◽

High Antitumor Activity

In this study, we prepared using low molecular weight water-soluble chitosan nanoparticle loaded paclitaxel (LMWSC-NPT) and investigated the potential as a drug carrier which is able to accumulate in the tumor site. In the experiment of receptor-mediated endocytosis, LMWSC-NPT was treated with sodium azid (NaN3) as an inhibitor of endocytosis process. As results, the antitumor activity of LMWSC-NPT treated with sodium azid didn’t show but LMWSC-NPT was shown the high antitumor activity. Therefore, LMWSC-NPs modified with hydrophobic group will be useful anticancer agent carrier via receptor-mediated endocytosis.

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Design, Synthesis and Anticancer Activity of Arylketo alkyne Derivatives of 7-Azaindole-oxazole

Chemical Data Collections ◽

10.1016/j.cdc.2021.100743 ◽

2021 ◽

pp. 100743

Author(s):

A.M.S. Krishna ◽

Hima Bindu Gandham ◽

Krishna Reddy Valluru ◽

N.S. Kameswara Rao ◽

Gattu Sridhar ◽

...

Keyword(s):

Anticancer Activity ◽

Design Synthesis ◽

Derivatives Of ◽

Alkyne Derivatives

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Synthesis, Characterization, and Antitumor Activity of Water-Soluble (Arene)ruthenium(II) Derivatives of 1,3-Dimethyl-4-acylpyrazolon-5-ato Ligands. First Example of Ru(arene)(ligand) Antitumor Species Involving Simultaneous Ru–N7(guanine) Bonding and Ligand Intercalation to DNA

Inorganic Chemistry ◽

10.1021/ic403170y ◽

2014 ◽

Vol 53 (7) ◽

pp. 3668-3677 ◽

Cited By ~ 32

Author(s):

Francesco Caruso ◽

Elena Monti ◽

Julian Matthews ◽

Miriam Rossi ◽

Marzia Bruna Gariboldi ◽

...

Keyword(s):

Antitumor Activity ◽

Water Soluble ◽

Arene Ligand ◽

Derivatives Of

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Clinical development of namitecan (ST1968), a novel camptothecin derivative with high antitumor activity: Phase I clinical data

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.2570 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 2570-2570 ◽

Cited By ~ 1

Author(s):

D. Hess ◽

S. Boehm ◽

A. Delmonte ◽

E. Gallerani ◽

P. Barbieri ◽

...

Keyword(s):

Antitumor Activity ◽

Maximum Tolerated Dose ◽

Water Soluble ◽

Hematologic Toxicity ◽

Cohort Design ◽

Blood And Urine Samples ◽

High Antitumor Activity ◽

Grade 3 ◽

Dose Levels ◽

Dose Limiting Toxicity

2570 Background: Namitecan is a new water-soluble camptothecin analogue which showed high antitumor activity in preclinical models. Aim of this trial was to determine safety, PK profile and activity in adult patients with advanced solid tumors. Methods: The dose escalation started at 2.5 mg i.v. on days 1 and 8 of a 21 day cycle (D1, D8 Q21D) and increased according to 3+3 cohort design depending on the observed toxicity. Dose limiting toxicity (DLT) definitions were: ANC <0.5x109/L for >5 days; PLT ≥ Grade 3 (CTC V3); grade ≥2 liver/renal toxicity not recovered by D22; any non-hematologic toxicity ≥ Grade 3; D8 dose skipping due to toxicity. Maximum tolerated dose (MTD) and recommended dose (RD) were the primary end-points. Blood and urine samples were collected at cycle 1 for PK evaluation. Results: 31 pts (11 endometrial ca., 5 CRC, 5 ovarian ca., 2 NSCLC, 8 other) have been included, with 6 dose levels evaluated (2.5; 5; 10; 15; 17.5 and 20 mg). 17.5 mg was introduced later when 2/7 DLTs at 20 mg were observed (ANC G4>5days, one with D8 skipping). At 17.5mg 2/4 pts experienced DLTs (ANC G4; D8 skipped). Uncomplicated neutropenia and thrombocytopenia were the most relevant G3/4 hematological toxicities. Other toxicities were mild or moderate asthenia, fatigue and alopecia. The MTD was defined at 17.5 mg and the RD was 15 mg. Stable disease ≥ 6 cycles was recorded in 6 pts (2 stable diseases ≥ 10 cycles). PK was linear and data suggest an entero-hepatic recirculation. No metabolites were found in plasma and the product resulted poorly excreted into urine. Conclusions: The MTD and RD of D1, D8 Q21D schedule have been identified. The study will continue with the evaluation of MTD and RD of a single administration per cycle (D1 Q21D), to optimize the schedule of treatment. [Table: see text]

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