Design, Synthesis and Analysis of Anticancer Activity of New Sar-Based  S16020 Derivatives

Tylińska, Beata; Jasztold‐Howorko, Ryszard; Kowalczewska, Karina; Szczaurska-Nowak, Katarzyna; Gębarowski, Tomasz; Wietrzyk, Joanna

doi:10.32383/appdr/89921

Cited by 6 publications

(4 citation statements)

References 14 publications

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“…The most recognized drugs based on analogs of pyrimidines are antibacterial (sulfadiazine, trimethoprim), antiviral (trifluridine, idoxuridine), anti-malarial (sulfadoxine), anti-HIV (Retrovir (zidovudine), stavudine), anti-tuberculosis (viomycin), anticancer (5-fluorouracil) agents. The data also show that the adjunction of a [(dialkylamino)alkyl]amino or (hydroxyalkyl)amino side chain enhances anticancer activity of compounds [ 8 , 9 , 10 , 11 ]. There are also studies on novel derivatives with a 3,4-dihydronaphthalen moiety that exhibit anticancer activity [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 84%

Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study

Tylińska

Wiatrak

Czyżnikowska

et al. 2021

IJMS

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In the present paper, new pyrimidine derivatives were designed, synthesized and analyzed in terms of their anticancer properties. The tested compounds were evaluated in vitro for their antitumor activity. The cytotoxic effect on normal human dermal fibroblasts (NHDF) was also determined. According to the results, all the tested compounds exhibited inhibitory activity on the proliferation of all lines of cancer cells (colon adenocarcinoma (LoVo), resistant colon adenocarcinoma (LoVo/DX), breast cancer (MCF-7), lung cancer (A549), cervical cancer (HeLa), human leukemic lymphoblasts (CCRF-CEM) and human monocytic (THP-1)). In particular, their feature stronger influence on the activity of P-glycoprotein of cell cultures resistant to doxorubicin than doxorubicin. Tested compounds have more lipophilic character than doxorubicin, which determines their affinity for the molecular target and passive transport through biological membranes. Moreover, the inhibitory potential against topoisomerase II and DNA intercalating properties of synthesized compounds were analyzed via molecular docking.

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Section: Introductionmentioning

confidence: 84%

Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study

Tylińska

Wiatrak

Czyżnikowska

et al. 2021

IJMS

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“…It is the only compound that has a methylhydroxy moiety at the 1-position, whereas the rest of the derivatives used in this study have alkylamino moieties at this position. Both modifications at 1-position improve hydrophilic properties of derivatives in comparison to the ellipticine, so the solubility in water is better [25]. Substitution at the 9-position seems to be a crucial factor for prooxidative activity since compounds with a methoxy group (1, 2, and 3) at this position displayed higher intracellular ROS levels when incubated with colorectal cancer cells than compound 4, which has a hydroxy group.…”

Section: Biological Evaluationmentioning

confidence: 99%

Antitumor Activity of New Olivacine Derivatives

et al. 2020

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Olivacine is an alkaloid-containing pyridocarbazole structure. It is isolated from the bark of the evergreen timber tree, Aspidosperma olivaceum. Its well-documented anticancer activity led to the synthesis of new derivatives, which are semisynthetic and fully synthetic pyridocarbazoles. This study aimed to evaluate the potential antineoplastic activity of four newly synthesized olivacine derivatives. Multidrug resistance is a common phenomenon causing failure in the chemotherapy of many tumors. It is mainly related to increased function of P-glycoprotein, an efflux pump removing cytostatic out of the cells. The cell lines used in the study were colorectal carcinoma cell lines: LoVo (doxorubicin-sensitive) and LoVo/DX (doxorubicin-resistant). The NHDF cell line was used to assess cell viability. First, the cells were incubated with olivacine derivatives. In the next step, the following assays were performed: DCF-DA assay, MTT assay, rhodamine 123 assay, detection of apoptosis, proliferation inhibition-mitotic index. The tested compounds showed higher antineoplastic potential and lower toxicity than the reference compound ellipticine. The results indicate that the new olivacine derivatives are good candidates for future anticancer drugs.

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“… Tyrosine Kinase Inhibition: Tyrosine kinases are enzymes that play a role in cell signaling and cancer progression. Some pyrimidine derivatives, such as imatinib (Gleevec), are tyrosine kinase inhibitors that have been successful in treating specific types of cancer, such as chronic myeloid leukemia (CML) [36].  Combination Therapies: Pyrimidine derivatives are often used in combination with other chemotherapy agents or targeted therapies to enhance their anticancer effects.…”

Section: Anticancer Activity Of Pyrimidine Derivativesmentioning

confidence: 99%

Pyrimidine derivatives: Their significance in the battle against malaria, cancer and viral infections

Sushma Somkuwar,

Neelesh Chaubey

2023

GSC Biol. Pharm. Sci.

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Pyrimidine derivatives play a significant role in combating viral infections, malaria, and cancer due to their diverse pharmacological properties. Pyrimidine derivatives, particularly nucleoside analogs, have been widely used as antiviral agents. They interfere with viral replication by inhibiting DNA or RNA synthesis.Examples include drugs like acyclovir (used against herpes viruses), lamivudine (for HIV and hepatitis B), and remdesivir (for COVID-19). These compounds help to manage and treat various viral infections, reducing their severity and spread. Pyrimidine derivatives are key components of antimalarial drugs like pyrimethamine and proguanil. They target the parasite Plasmodium falciparum's dihydrofolate reductase enzyme, essential for its survival. These drugs have been instrumental in combating malaria, a major global health concern, by inhibiting the growth of the malaria parasite within the human body. Pyrimidine analogs are used in chemotherapy to target rapidly dividing cancer cells. Drugs like 5-fluorouracil (5-FU) and cytarabine inhibit DNA synthesis in cancer cells, leading to cell death. These derivatives have been crucial in the treatment of various cancers, helping to slow down tumor growth and improve patient outcomes. Overall, this article aims to consolidate existing knowledge on the topic, synthesize relevant information, and contribute to a better understanding of the potential applications of pyrimidine derivatives in the fields of oncology, virology, and tropical medicine.

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Design, Synthesis and Analysis of Anticancer Activity of New Sar-Based S16020 Derivatives

Cited by 6 publications

References 14 publications

Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study

Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis, Biological Evaluation and Molecular Docking Study

Antitumor Activity of New Olivacine Derivatives

Pyrimidine derivatives: Their significance in the battle against malaria, cancer and viral infections

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