Synthesis of New 4-Thiazolidinone-, Pyrazoline-, and Isatin-Based Conjugates with Promising Antitumor Activity

Abstract

The synthesis and antitumor activity screening of novel 3-[2-(3,5-diaryl-4,5-dihydropyrazol-1-yl)-4-oxo-4,5-dihydro-1,3-thiazol-5-ylidene]-2,3-dihydro-1H-indol-2-ones 1-23 and 3-(3,5-diarylpyrazol-1-yl)-2,3-dihydro-1H-indol-2-ones 24-39 are performed. In vitro anticancer activity of the synthesized compounds was tested by the National Cancer Institute. Most of them displayed anticancer activity on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancers cell lines. The structure-activity relationship is discussed. The most effective anticancer compound 10 was found to be active with mean GI₅₀ and TGI values of 0.071 μM and 0.76 μM, respectively. It demonstrated the highest antiproliferative influence on the non-small-cell lung cancer cell line HOP-92 (GI₅₀ < 0.01 μM), colon cancer line HCT-116 (GI₅₀ = 0.018 μM), CNS cancer cell line SNB-75 (GI₅₀ = 0.0159 μM), ovarian cancer cell line NCI/ADR-RES (GI₅₀ = 0.0169 μM), and renal cancer cell line RXF 393 (GI₅₀ = 0.0197 μM).

Biochemical indicators of nephrotoxicity in blood serum of rats treated with novel 4-thiazolidinone derivatives or their complexes with polyethylene glycol-containing nanoscale polymeric carrier

“…Compounds denoted as 3882, 3288, 3833 were synthesized at the Department of Pharmaceuticals, Organic and Bioorganic Chemistry at Danylo Halytsky Lviv National Medical University [10]. Doxorubicin (Arterium, Ukraine) was of standard pharmacy distribution.…”

Indicators of oxidative and nitrosative stress and activity of enzymes of nitric oxide metabolism in rats treated with 4-thiazolidinone derivatives possessing antineoplastic activity

“…The heterocyclic 4-thiazolidinones derivatives (Les-3288, Les-3882 and Les-3833) were synthesized as described earlier [15,17]. These compounds were dissolved in the dimethylsulfoxide (DMSO, Arterium, Ukraine), and then additionally dissolved in the distilled water before use.…”

“…The aim of our study was to measure the content of metabolites of the oxidative and nitrosative stress, as well as the activity of enzymes of nitric oxide metabolism in blood serum of laboratory rats treated with 4-thiazolidinone derivatives that were previously studied at the National Cancer Institute (USA) within DPT program [15]. Cytotoxicity of the above mentioned compounds towards 60 human tumor cell lines has been evaluated, and three compounds (Les-3288, Les-3833 and Les-3882) posses sing high cytotoxic action towards tumor cells were selected for more detailed analysis of the perspectives of their use as the antineoplastic agents.…”

Synthesis of 1-phenyl-3-(4’-nitrophenyl)-5-(3’,4’-dimethoxy-6’-nitrophenyl)-2-pyrazoline and its antibacterial activity

“…Pyrazole and pyrazoline are important nitrogen containing 5-membered heterocyclic compound. Pyrazoline which is well known as pyrazole derivative or 4,5-dihydropyrazole is reported possess a broad spectrum of biological activities such as anticonvulsant [2], antimicrobial [1,3,8], antiamoebic [3], analgesic [1], anti-inflammmatory [1], antidepressant [4], anxiogenic [4], inhibitors of monoamine oxidase [4], fungisical [5], insecticidal [5], antitumor [6], and antinociceptive [7]. Therefore, the prevalence of pyrazole core in biologically active molecules has stimulated the need for elegant and efficient ways to make these heterocyclic lead.…”