Influence of chlorine substituents on biological activity of chemicals

Naumann, Klaus

doi:10.1002/(sici)1521-3897(199907)341:5<417::aid-prac417>3.0.co;2-a

Cited by 45 publications

(13 citation statements)

References 16 publications

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“…These results are supported by the bibliographic information where the 1,2,3-triazoles are important five-membered heterocyclic scaffold strongly associated with many biological activities [42]. On the other hand, over time, it has been found empirically that the introduction of a chlorine atom into one or more specific positions of a biologically active molecule may substantially improve the intrinsic biological activity [43].. Compounds 1a and 3d showed the best performance in relation to Emax values; all of them are close to 0.1 for each cancer cell lines tested.…”

Section: Ec50 Determination On Myrtenyl Derivativessupporting

confidence: 58%

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Synthesis and Cytotoxic Analysis of Novel Myrtenyl Grafted Pseudo-Peptides Revealed Potential Candidates for Anticancer Therapy

et al. 2020

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Myrtenal is a natural monoterpene isolated from essential oils of several plants and their derivates have shown to have several biological properties including cytotoxicity. The cytotoxic activity of these derivates are being investigated for their antitumor effect leading to the development of potential anticancer agents. In this study, novels Myrtenyl grafted pseudo-peptides were designed, synthesized and functionally characterized as possible therapeutic agents for cancer treatment. Thirteen novel Myrtenyl grafted pseudo-peptides were prepared in high atom economy and efficiency by a classic Ugi-4CR and sequential post-modification. Their structures were confirmed by NMR, and ESI-MS, and its cytotoxic activity was evaluated in three cancer cell lines and primary CD4+ T cells at different proliferative cycles. Our results revealed that some of these compounds showed significant cytotoxicity against human gastric, breast and colon adenocarcinoma cells lines, but not against human dermal fibroblast cell line. Moreover, from the thirteen novel myrtenyl synthesized the compound (1R,5S)-N-{[1-(3-chlorophenyl)-1H-1,2,3-triazol-4-yl]methyl}-N-[2-(cyclohexylamino)-2–oxoethyl]-6,6-dimethylbicyclo[3.1.1]hept-2-ene-2-carboxamide (3b) proved to be the best candidate in terms of acceptable EC50, and Emax values in cancer cell lines and at inducing cytotoxicity in CD4+ T cells undergoing active proliferation, without affecting non-proliferating T cells. Overall, the synthesis and characterization of our Myrtenyl derivates revealed novel potential anticancer candidates with selective cytotoxic activity.

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Section: Ec50 Determination On Myrtenyl Derivativessupporting

confidence: 58%

“…) 13. C NMR (100 MHz, MeOD) δ 174 43,. 169.67, 145.85, 144.04, 139.46, 136.60, 132.45, 129.97, 128.65, 123.31, 121.63, 119.80, 49.93, 45.49, 41.71, 38.86, 33.69, 32.79, 26.59, 26.34, 26.01, 21.56.…”

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confidence: 99%

Synthesis and Cytotoxic Analysis of Novel Myrtenyl Grafted Pseudo-Peptides Revealed Potential Candidates for Anticancer Therapy

et al. 2020

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“…This facilitates its reaction with bionucleophiles such as DNA bases or a regulating protein through the displacement of chlorine. It acts as a starting point for mutations in cancer regulating targets; hence, this chemistry is effectively used for chemotherapy against cancer [11]. Studies on the biological activity of fluorine substitution have revealed that the C-F bond (van der Waals radius = 1.47 Å) has amore similar bond length tothat of the C-O bond (van der Waals radius = 1.52 Å) than to that ofthe C-H bond (van der Waals radius = 1.2 Å); hence, it can be considered as isosteric with oxygen.…”

Section: Introductionmentioning

confidence: 99%

N-(3-Chloro-2-methylphenyl)-4-(4-fluorophenyl)-1,3-thiazol-2-amine

Uwabagira

Sarojini

Poojary

2018

Molbank

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The two precursors 3-chloro-2-methylphenylthiourea 2 and 4-fluorophenacyl bromide 4 are reacted under Hantzsch thiazole synthesis condition to yield the new compound N-(3-chloro-2-methylphenyl)-4-(4-fluorophenyl)-1,3-thiazol-2-amine 5. The IR, 1 H-NMR, 13 C-NMR and mass spectral data are presented, along with its in vitro antibacterial activity against Staphylococcus aureus and Chromobacterium violaceum.

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“…Hence, the internal heavy atom effect accelerates the S 1 →T 1 intersystem-crossing rate, increases the triplet quantum yields (Φ T ) of photosensitizers and consequently improves the ability to generate ROSs. In addition, the introduction of fluorine and chlorine atoms into the PS structure leads to a change in their polarity, which in turn can increase the rate of transport of biologically-active compounds through lipid membranes [29][30][31][32][33][34].It is widely recognized that PDT regimes can trigger rapid inflammatory responses that are essential for the activation of antitumor immunity [35][36][37], improving long-term tumor control and offering protection against metastasis [38]. Unlike most chemotherapies, which mainly lead to apoptotic cell death, PDT may also lead to necrosis or immunogenic cell death (ICD), which can result in controlled inflammation, which in turn leads to further stimulation of the immune system [7,37,[39][40][41].…”

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confidence: 99%

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confidence: 99%

Lipophilicity of Bacteriochlorin-Based Photosensitizers as a Determinant for PDT Optimization through the Modulation of the Inflammatory Mediators

Pucelik

Arnaut

Dąbrowski

2019

JCM

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Photodynamic therapy (PDT) augments the host antitumor immune response, but the role of the PDT effect on the tumor microenvironment in dependence on the type of photosensitizer and/or therapeutic protocols has not been clearly elucidated. We employed three bacteriochlorins (F 2 BOH, F 2 BMet and Cl 2 BHep) of different polarity that absorb near-infrared light (NIR) and generated a large amount of reactive oxygen species (ROS) to compare the PDT efficacy after various drug-to-light intervals: 15 min. (V-PDT), 3h (E-PDT) and 72h (C-PDT). We also performed the analysis of the molecular mechanisms of PDT crucial for the generation of the long-lasting antitumor immune response. PDT-induced damage affected the integrity of the host tissue and developed acute (protocol-dependent) local inflammation, which in turn led to the infiltration of neutrophils and macrophages. In order to further confirm this hypothesis, a number of proteins in the plasma of PDT-treated mice were identified. Among a wide range of cytokines (IL-6, IL-10, IL-13, IL-15, TNF-α, GM-CSF), chemokines (KC, MCP-1, MIP1α, MIP1β, MIP2) and growth factors (VEGF) released after PDT, an important role was assigned to IL-6. PDT protocols optimized for studied bacteriochlorins led to a significant increase in the survival rate of BALB/c mice bearing CT26 tumors, but each photosensitizer (PS) was more or less potent, depending on the applied DLI (15 min, 3 h or 72 h). Hydrophilic (F 2 BOH) and amphiphilic (F 2 BMet) PSs were equally effective in V-PDT (>80 cure rate). F 2 BMet was the most efficient in E-PDT (DLI = 3h), leading to a cure of 65 % of the animals. Finally, the most powerful PS in the C-PDT (DLI = 72 h) regimen turned out to be the most hydrophobic compound (Cl 2 BHep), allowing 100 % of treated animals to be cured at a light dose of only 45 J/cm 2 .In practice, three fundamental PDT approaches are investigated: vascular-targeted PDT (V-PDT), tumor cellular-targeted PDT (C-PDT) and endothelial cells-targeted PDT (E-PDT). V-PDT is characterized by short drug-to-light intervals (DLI = 5-15 min). The main target of this protocol is the tumor vascularization. C-PDT targets tumour cells directly through specific molecules on cancer cells' surfaces. In this case, longer drug-to-light intervals (DLI > 12h) are used [8][9][10][11]. At intermediate DLIs (e.g., 3 h) the PS is found mainly in the blood and endothelial cells, with partial accumulation in tumor cells [6,12], and protocols using such intermediate DLIs are designated here as E-PDT.The first step in PDT is the selection of a PS with physicochemical and pharmacological properties adequate for the intended PDT regime [13]. The hydrophilicity/lipophilicity of the PS is one of the most important factors influencing its biological behavior, including uptake by cancer cells, intracellular localization, biodistribution and pharmacokinetics [14,15]. The high expression of low-density lipoprotein (LDL) receptors in tumors makes LDL-bounded lipophilic PSs more likely to achieve LDL-receptor-mediated endocyt...

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Influence of chlorine substituents on biological activity of chemicals

Cited by 45 publications

References 16 publications

Synthesis and Cytotoxic Analysis of Novel Myrtenyl Grafted Pseudo-Peptides Revealed Potential Candidates for Anticancer Therapy

Synthesis and Cytotoxic Analysis of Novel Myrtenyl Grafted Pseudo-Peptides Revealed Potential Candidates for Anticancer Therapy

N-(3-Chloro-2-methylphenyl)-4-(4-fluorophenyl)-1,3-thiazol-2-amine

Lipophilicity of Bacteriochlorin-Based Photosensitizers as a Determinant for PDT Optimization through the Modulation of the Inflammatory Mediators

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