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1.
Eur J Med Chem ; 236: 114357, 2022 Jun 05.
Article in English | MEDLINE | ID: mdl-35428012

ABSTRACT

NLRP3 inflammasome activation plays a key role in a variety of inflammatory diseases as IBD. Here a series of pterostilbene derivatives were designed and synthesized based on previous SAR, leading to discovery of new effective NLRP3 inflammasome inhibitors with metabolic stability. Among them, the most effective compound 27 showed high inhibitory efficacy (against IL-1 ß: IC50 = 1.23 µM) and almost no toxicity (against L02: IC50 > 100 µM). Further mechanism studies have shown that compound 27 directly targets the NLRP3 and affects the assembly of inflammasomes to inhibit the activation of NLRP3 inflammasomes. More importantly, in vitro experiments show that compound 27 has a significant therapeutic effect on DSS-induced colitis in mice with good metabolic stability to liver microsomes (t1/2 = 138.6 min). This research encourages the further development of more effective NLRP3 inflammasome inhibitors based on this chemical scaffold.


Subject(s)
Colitis , Inflammasomes , Aniline Compounds/therapeutic use , Animals , Cell Line , Colitis/chemically induced , Colitis/drug therapy , Mice , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
2.
J Med Chem ; 64(18): 13633-13657, 2021 09 23.
Article in English | MEDLINE | ID: mdl-34506712

ABSTRACT

Studies have shown that the abnormal activation of the NLRP3 inflammasome is involved in a variety of inflammatory-based diseases. In this study, a high content screening model targeting the activation of inflammasome was first established and pterostilbene was discovered as the active scaffold. Based on this finding, total of 50 pterostilbene derivatives were then designed and synthesized. Among them, compound 47 was found to be the best one for inhibiting cell pyroptosis [inhibitory rate (IR) = 73.09% at 10 µM], showing low toxicity and high efficiency [against interleukin-1ß (IL-1ß): half-maximal inhibitory concentration (IC50) = 0.56 µM]. Further studies showed that compound 47 affected the assembly of the NLRP3 inflammasomes by targeting NLRP3. The in vivo biological activity showed that this compound significantly alleviated dextran sodium sulfate (DSS)-induced colitis in mice. In general, our study provided a novel lead compound directly targeting the NLRP3 protein, which is worthy of further research and structural optimization.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Colitis/drug therapy , Inflammasomes/antagonists & inhibitors , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , Stilbenes/therapeutic use , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/toxicity , Cell Line , Colitis/chemically induced , Dextran Sulfate , Female , Humans , Interleukin-1beta/antagonists & inhibitors , Macrophages/drug effects , Male , Mice, Inbred C57BL , Molecular Structure , Pyroptosis/drug effects , Stilbenes/chemical synthesis , Stilbenes/toxicity , Structure-Activity Relationship
3.
Eur J Med Chem ; 213: 113174, 2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33515864

ABSTRACT

In order to discover and develop drug-like anti-inflammatory agents against arthritis, based on "Hit" we found earlier and to overcome drawbacks of toxicity, twelve series of total 89 novel pyrimidine, pyrazolo[4,3-d]pyrimidine and thieno[3,2-d]pyrimidine derivatives were designed, synthesized and screened for their anti-inflammatory activity against NO and toxicity for normal liver cells (LO2). Relationships of balance toxicity and activity have been summarized through multi-steps, and title compounds 22o, 22l were found to show lower toxicity (against LO2: IC50 = 2934, 2301 µM, respectively) and potent effect against NO release (IR = 98.3, 97.67%, at 10 µM, respectively). Furthermore, compound 22o showed potent iNOS inhibitory activity with value of IC50 is 0.96 µM and could interfere stability and formation of the active dimeric iNOS. It's anti-inflammatory activity in vivo was assessed by AIA rat model. Furthermore, the results of metabolic stability, CYP, PK study in vivo, acute toxicity study and subacute toxicity assessment indicated this compound had good drug-like properties for treatment.


Subject(s)
Arthritis/drug therapy , Drug Development , Enzyme Inhibitors/pharmacology , Nitric Oxide Synthase Type II/antagonists & inhibitors , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Administration, Oral , Animals , Arthritis/metabolism , Cells, Cultured , Dimerization , Disease Models, Animal , Dose-Response Relationship, Drug , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/chemistry , Freund's Adjuvant , Humans , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Male , Mice , Molecular Structure , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/metabolism , Pyrazoles/administration & dosage , Pyrazoles/chemistry , Pyrimidines/administration & dosage , Pyrimidines/chemistry , RAW 264.7 Cells , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship
4.
Eur J Med Chem ; 206: 112722, 2020 Nov 15.
Article in English | MEDLINE | ID: mdl-32823004

ABSTRACT

Phthalide is a promising chemical scaffold and has been proved to show potent anti-inflammatory efficacy. In this study, three series, total of 31 novel phthalide derivatives were designed and synthesized, their anti-inflammatory activities were screened in vitro and in vivo. The anti-inflammatory activity of all the compounds were screened on LPS induced NO production to evaluating their inhibitory effects. Structure-activity relationship has been concluded, and finally 3-((4-((4-fluorobenzyl)oxy)phenyl)(hydroxy)methyl)-5,7-dimethoxyisobenzofuran-1 (3H)-one (compound 9o) was found to be the active one with low toxicity, which showed 95.23% inhibitory rate at 10 µM with IC50 value of 0.76 µM against LPS-induced NO over expression. Preliminary mechanism studies indicated that compound 9o activated Nrf2/HO-1 signaling pathway via accumulation ROS and blocks the NF-κB/MAPK signaling pathway. The in vivo anti-inflammatory activity shown that compound 9o had obvious therapeutic effect against the adjuvant-induced rat arthritis model.


Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/pharmacology , Benzofurans/chemical synthesis , Benzofurans/pharmacology , Animals , Anti-Inflammatory Agents/chemistry , Benzofurans/chemistry , Chemistry Techniques, Synthetic , Inhibitory Concentration 50 , MAP Kinase Signaling System/drug effects , Mice , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , RAW 264.7 Cells , Reactive Oxygen Species/metabolism
5.
Bioorg Chem ; 96: 103597, 2020 03.
Article in English | MEDLINE | ID: mdl-32028063

ABSTRACT

Some important pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α and nitric oxide are thought to play key roles in the destruction of cartilage and bone tissue in joints affected by rheumatoid arthritis. In the present study, a series of new myricetin-pentadienone hybrids were designed and synthesized. Majority of them effectively inhibited the expressions liposaccharide-induced secretion of IL-6, TNF-α and NO in RAW264.7. The most prominent compound 5o could significantly decrease production of above inflammatory factors with IC50 values of 5.22 µM, 8.22 µM and 9.31 µM, respectively. Preliminary mechanism studies indicated that it could inhibit the expression of thioredoxin reductase, resulting in inhibiting of cell signaling pathway nuclear factor (N-κB) and mitogen-activated protein kinases. Significantly, compound 5o was found to effectively inhibit Freund's complete adjuvant induced rat adjuvant arthritis in vivo.


Subject(s)
Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Flavonoids/chemistry , Flavonoids/pharmacology , Alkadienes/chemical synthesis , Alkadienes/chemistry , Alkadienes/pharmacology , Animals , Anti-Inflammatory Agents/chemical synthesis , Arthritis, Experimental/drug therapy , Arthritis, Experimental/metabolism , Chemistry Techniques, Synthetic , Flavonoids/chemical synthesis , Interleukin-6/antagonists & inhibitors , Interleukin-6/metabolism , Male , Mice , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/metabolism , RAW 264.7 Cells , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/metabolism
6.
J Enzyme Inhib Med Chem ; 34(1): 1678-1689, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31530032

ABSTRACT

A series of novel 4-ferrocenylchroman-2-one derivatives were designed and synthesised to discover potent anti-inflammatory agents for treatment of arthritis. All the target compounds had been screened for their anti-inflammatory activity by evaluating the inhibition effect of LPS-induced NO production in RAW 264.7 macrophages. Among them, 4-ferrocenyl-3,4-dihydro-2H-benzo[g]chromen-2-one (3h) was found to be the most potent compound in inhibiting the productions of NO with low toxicity. This compound also exhibited significant inhibition of the productions of IL-6 and TNF-α in RAW 264.7 macrophages. Preliminary mechanism studies indicated that compound 3h could inhibit the activation of LPS-induced NF-κB and MAPKs signalling pathways. The in vivo anti-inflammatory effect of this compound was determined in the rat adjuvant-induced arthritis model.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arthritis/drug therapy , Chromones/pharmacology , Interleukin-6/antagonists & inhibitors , Mitogen-Activated Protein Kinases/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Arthritis/metabolism , Cell Survival/drug effects , Chromones/chemical synthesis , Chromones/chemistry , Dose-Response Relationship, Drug , Freund's Adjuvant , Interleukin-6/biosynthesis , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Male , Mice , Mitogen-Activated Protein Kinases/metabolism , Molecular Structure , NF-kappa B/metabolism , RAW 264.7 Cells , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/biosynthesis
7.
Eur J Med Chem ; 175: 114-128, 2019 Aug 01.
Article in English | MEDLINE | ID: mdl-31077997

ABSTRACT

In order to discover novel anti-inflammatory agents, total thirty-seven new resveratrol-based flavonol derivatives were designed and synthesized. All compounds have been screened for their anti-inflammatory activity by evaluating their inhibition effect of LPS-induced NO production in RAW 264.7 macrophages. Their toxicity was also assessed in vitro. Structure-activity relationships (SARs) have been concluded, and finally 2-(2,4-dimethoxy-6-(4-methoxystyryl)phenyl)-3-hydroxy-4H-chromen-4-one was found to be the most active scaffold with low toxicity. This compound could significantly decrease productions of NO, IL-6 and TNF-α with IC50 values of 1.35, 1.12 and 1.92 µM, respectively in RAW 264.7 macrophages. Preliminary mechanism studies indicated that it could inhibit the expression of TLR4 protein, resulting in activation of the NF-ĸB cell signaling pathway. The in vivo anti-inflammatory activity of this compound could reduce pulmonary inflammation by mouse model of LPS-induced acute lung injury (ALI). We believe these findings would further support studies of rational design of more efficient acute lung injury regulatory inhibitors.


Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/pharmacology , Flavonoids/chemical synthesis , Flavonoids/pharmacology , Interleukin-6/antagonists & inhibitors , Nitric Oxide/antagonists & inhibitors , Resveratrol/chemistry , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Anti-Inflammatory Agents/toxicity , Flavonoids/chemistry , Flavonoids/toxicity , In Vitro Techniques , Inhibitory Concentration 50 , Lipopolysaccharides/toxicity , MAP Kinase Signaling System/drug effects , Mice , Molecular Docking Simulation , NF-kappa B/metabolism , RAW 264.7 Cells , Structure-Activity Relationship , p38 Mitogen-Activated Protein Kinases/metabolism
8.
J Enzyme Inhib Med Chem ; 34(1): 1121-1130, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31117832

ABSTRACT

Four series of total 35 new pyrazolo[4,3-d]pyrimidine compounds were designed, synthesized and evaluated for their inhibitory activity against LPS-induced NO production in RAW264.7 macrophages. Among them, compound 4e was found to be the most potent inhibitor, which decreased the production of cytokines in vitro, such as NO, IL-6 and TNF-α, with IC50 values of 2.64, 4.38 and 5.63 µM, respectively. Further studies showed that compound 4e inhibited cytokines secretion of macrophages through suppressing TLR4/p38 signaling pathway. Additionally, compound 4e showed in vivo anti-inflammatory activity in LPS-induced model of acute lung injury. These data suggested that compound 4e may be a promising lead structure for the treatment of ALI.


Subject(s)
Acute Lung Injury/drug therapy , Drug Design , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Animals , Cell Survival/drug effects , Cells, Cultured , Cytokines/antagonists & inhibitors , Cytokines/metabolism , Dose-Response Relationship, Drug , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Male , Mice , Mice, Inbred C57BL , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/metabolism , Pyrazoles/chemical synthesis , Pyrazoles/chemistry , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , RAW 264.7 Cells , Signal Transduction/drug effects , Structure-Activity Relationship
9.
J Med Chem ; 62(8): 4013-4031, 2019 04 25.
Article in English | MEDLINE | ID: mdl-30925056

ABSTRACT

In order to discover novel anti-inflammatory agents for treatment of arthritis and based on preliminary structure-activity relationships, four series (A-D) of total 90 new pyrazolo[4,3- d]pyrimidine compounds were designed and synthesized. All the compounds have been tested for their anti-inflammatory activities by inhibiting of LPS-induced NO production. A clear structure-activity relationship has been concluded step by step, and finally 3,4,5-trimethoxystyryl-1 H-pyrazolo[4,3- d]pyrimidine was found to be the most active scaffold. Among them, compound D27 was discovered as the most potent anti-inflammatory agent (IC50 = 3.17 µM) with low toxicity and strong inhibitory of NO release (IR = 90.4% at 10 µM). This compound also showed potent inhibition of iNOS with IC50 value of 1.12 µM. Preliminary mechanism studies indicated that it could interfere with the stability and formation of active dimeric iNOS. The anti-inflammatory effect of this compound was determined by adjuvant-induced arthritis in rat model. We believe these findings would further support the study of rational design of more efficient iNOS inhibitors in the future.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Arthritis, Experimental/drug therapy , Enzyme Inhibitors/chemistry , Nitric Oxide Synthase Type II/antagonists & inhibitors , Pyrazoles/chemistry , Pyridines/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/pharmacology , Arthritis, Experimental/pathology , Crystallography, X-Ray , Dimerization , Disease Models, Animal , Drug Design , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/therapeutic use , Interleukin-1beta/metabolism , Lipopolysaccharides/toxicity , Macrophages/cytology , Macrophages/drug effects , Macrophages/metabolism , Mice , Molecular Conformation , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism , Pyrazoles/metabolism , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Pyridines/metabolism , Pyridines/pharmacology , Pyridines/therapeutic use , RAW 264.7 Cells , Rats , Structure-Activity Relationship
10.
J Enzyme Inhib Med Chem ; 33(1): 130-138, 2018 Dec.
Article in English | MEDLINE | ID: mdl-29199491

ABSTRACT

To develop novel anti-inflammatory agents, a series of new pentadienone oxime ester compounds were designed and synthesized. The structures were determined by IR, 1H NMR, 13 C NMR, and HRMS. All compounds have been screened for their anti-inflammatory activity by evaluating their inhibition against LPS-induced nitric oxide (NO) release in RAW 264.7 cell. Among them, compound 5j was found to be one of the most potent compounds in inhibiting NO and IL-6 (IC50 values were 6.66 µM and 5.07 µM, respectively). Preliminary mechanism studies show that title compound 5j could significantly suppress expressions of nitric oxide synthase, COX-2, and NO, IL-6 through Toll-like receptor 4/mitogen-activated protein kinases/NF-κB signalling pathway. These data support further studies to assess rational design of more efficient pentadienone oxime ester derivatives with anti-inflammatory activity in the future.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Esters/pharmacology , Ketones/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Nitric Oxide/antagonists & inhibitors , Oximes/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Dose-Response Relationship, Drug , Esters/chemistry , Ketones/chemistry , Lipopolysaccharides/pharmacology , Mice , Molecular Structure , Nitric Oxide/biosynthesis , Oximes/chemistry , RAW 264.7 Cells , Structure-Activity Relationship
11.
Cell Death Dis ; 8(8): e3016, 2017 08 24.
Article in English | MEDLINE | ID: mdl-28837145

ABSTRACT

Dominant-negative mutants of telomerase hTERT were demonstrated to have selective effects in tumor cells. However, no any effective and highly selective hTERT inhibitor has been developed so far. We focused on developing new hTERT modulators and synthesized a small molecular compound, named (4-bromophenyl)(3-hydroxy-4-methoxyphenyl)methanone. Our in vitro studies found that title compound showed high inhibitory activity against telomerase, had high antiproliferative capacity on SMMC-7721 cells with IC50 value 88 nm, and had no obvious toxic effect on human normal hepatocyte cells with IC50 value 10 µM. Our in vivo studies showed that this compound significantly inhibited tumor growth in xenograft tumor models. The further molecular mechanisms of title compound inhibition SMMC-7721 cell proliferation by modulating hTERT were explored; the results showed that endoplasmic reticulum stress (ERS) through ER over response (EOR) activates the expression of hTERT, and then induces ERS, which is believed to be intricately associated with oxidative stress and mitochondrial dysfunction, resulting in apoptotic cell death, thereby modulating the expression of downstream signaling molecules including CHOP (CAAT/enhancer-binding protein homologous protein)) and mitochondrion pathway of apoptosis, leading to inhibition of cell proliferation.


Subject(s)
Endoplasmic Reticulum Stress/drug effects , Indoles/therapeutic use , Telomerase/metabolism , Apoptosis , Cell Line, Tumor , Cell Proliferation , Humans , Indoles/pharmacology , Up-Regulation
12.
Eur J Med Chem ; 138: 170-181, 2017 Sep 29.
Article in English | MEDLINE | ID: mdl-28667873

ABSTRACT

To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of new phenyl-pyrazoline-coumarin derivatives (4a∼4m) were designed and synthesized. Compounds 4a and 4b were determined by X-ray crystallography. All of the compounds have been screened for their anti-inflammatory activity characterized by evaluating their inhibition against LPS-induced IL-6 release. Among them, compound 4m showed the highest anti-inflammatory activity with inhibiting IL-6, TNF-α and nitric oxide (NO) production lipopolysaccharide (LPS)-stimulated. The further study showed that title compound 4m could significantly suppress expressions of nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and the productions of IL-6, TNF-α, NO through NF-κB/MAPK signaling pathway. The anti-inflammatory activity of compound 4m was determined by carrageenan induced paw edema. Furthermore in vivo evaluation results indicated that compound 4m could inhibit AA-induced rat ankle joints.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Coumarins/pharmacology , Interleukin-6/antagonists & inhibitors , Nitric Oxide/antagonists & inhibitors , Pyrazoles/pharmacology , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Animals , Ankle Joint/drug effects , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Carrageenan , Cell Survival/drug effects , Cells, Cultured , Coumarins/chemistry , Crystallography, X-Ray , Dose-Response Relationship, Drug , Edema/chemically induced , Edema/drug therapy , Interleukin-6/biosynthesis , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Male , Mice , Models, Molecular , Molecular Structure , Nitric Oxide/biosynthesis , Pyrazoles/chemistry , RAW 264.7 Cells , Rats , Rats, Sprague-Dawley , Structure-Activity Relationship , Tumor Necrosis Factor-alpha/biosynthesis
13.
Bioorg Med Chem Lett ; 27(8): 1803-1807, 2017 04 15.
Article in English | MEDLINE | ID: mdl-28284806

ABSTRACT

A series of new (2E,4E)-1-(substitutedphenyl)-5-(substitutedphenyl)penta-2,4-dien-1-one derivatives were designed and synthesized. Compounds 3i, 3k were determined by X-ray. All of the compounds have been screened for their anti-inflammatory activity characterized by evaluating their inhibition against LPS-induced IL-6 and TNF-α release in cell RAW 264.7 stimulated with LPS. Compound 3i showed the highest anti-inflammatory activity on decreasing IL-6 and TNF-α. The further study showed that title compound 3i inhibited expression of proteins p-p65, iNOS, COX-2 LPS-induced. Immunofluorescence also revealed compound 3i could lightly reduce activation p65 in nuclei. These results indicate that compound 3i anti-inflammatory role may partly due to its inhibitory effect on the NF-κB signaling pathway.


Subject(s)
Alkadienes/chemistry , Alkadienes/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Curcumin/analogs & derivatives , Curcumin/pharmacology , Animals , Interleukin-6/immunology , Lipopolysaccharides/immunology , Macrophages/drug effects , Mice , Models, Molecular , RAW 264.7 Cells , Tumor Necrosis Factor-alpha/immunology
14.
Eur J Med Chem ; 124: 729-739, 2016 Nov 29.
Article in English | MEDLINE | ID: mdl-27639364

ABSTRACT

Based on telomerase, thirteen novel phenstatin moiety linked stavudine derivatives (8a∼8e and 11a∼11f) were synthesized. The structures were determined by NMR and TOF-HRMS. The screening results showed that some compounds had better anti-cancer activity in vivo and in vitro. Among them, Compound 8d showed high inhibitory activity against telomerase and showed good antiproliferative activity against SGC-7901 cell with IC50 value 0.77 µM by inducing cell cycle arrest at G2 phase. It also could improve SGC-7901 cell apoptosis, mitochondrial membrane potential assay indicated that the dissipation of MMP might participate in apoptosis induced by title compound. In vivo studies showed that compound 8d displayed potent anticancer activity with inhibition tumor growth.


Subject(s)
Benzophenones/chemical synthesis , Drug Design , Nucleosides/chemical synthesis , Telomerase/antagonists & inhibitors , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Benzophenones/chemistry , Benzophenones/pharmacology , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Enzyme Activation/drug effects , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , HeLa Cells , Humans , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Membrane Potential, Mitochondrial/drug effects , Molecular Structure , Nucleosides/chemistry , Nucleosides/pharmacology
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