Synthesis and cytotoxicity of novel 6,8,9-trisubstituted purine analogs against liver cancer cells.

A series of novel 6-(substituted phenyl piperazine)-8-(4-substituted phenyl)-9-cyclopentyl purines, 10-51, were synthesized by a four-step synthesis, achieving an overall yield of about 43 %. The reaction conditions were effectively optimized, and the final products were obtained with high purity and yield in all synthesis steps. The synthesized nucleobases were evaluated for their in vitro cytotoxic activities on selected human cancer cell lines (HUH7 (liver), HCT116 (colon), and MCF7 (breast)) using the Sulforhodamine B (SRB) assay.

Exploration of novel 6,8,9-trisubstituted purine analogues: synthesis, in vitro biological evaluation, and their effect on human cancer cells.

Cancer, a leading global cause of mortality, demands continuous advancements in therapeutic strategies. This study focuses on the design and synthesis of a novel series of purine derivatives, specifically 6-(substituted phenyl piperazine)-8-(4-phenoxyphenyl)-9-cyclopentyl purine derivatives (5-11). The motivation behind this endeavor lies in addressing acquired resistance mechanisms in cancer cells, a significant hurdle in current treatment modalities.

Newly synthesized 6-substituted piperazine/phenyl-9-cyclopentyl containing purine nucleobase analogs act as potent anticancer agents and induce apoptosis inhibiting Src in hepatocellular carcinoma cells.

Newly synthesized 6-substituted piperazine/phenyl-9-cyclopentyl-containing purine nucleobase analogs were tested for their anticancer activity against human cancer cells. Compounds 15, 17-24, 49, and 56 with IC values less than 10 μM were selected for further examination on an enlarged panel of liver cancer cell lines. Experiments revealed that compound 19 utilizes its high cytotoxic potential (IC < 5 μM) to induce apoptosis .

A Novel 6,8,9-Trisubstituted Purine Analogue Drives Breast Cancer Luminal A Subtype MCF-7 to Apoptosis and Senescence through Hsp70 Inhibition.

Background: Cancer cells restrain apoptotic and senescence pathways through intracellular heat shock protein 70 (Hsp 70). These cells aid stimulus-independent growth, and their higher metabolism rate requires Hsps. Hsps compensate abnormally increased substrate protein folding rate of cancer cells.

Entrectinib: A New Selective Tyrosine Kinase Inhibitor Approved for the Treatment of Pediatric and Adult Patients with NTRK Fusionpositive, Recurrent or Advanced Solid Tumors.

Background: Entrectinib is a highly potent ATP-competitive and selective inhibitor of tyrosine kinases - Trk A B C, ALK, and ROS1. It was developed by Roche and initially approved in Japan in 2019 to treat pediatric and adult patients with NTRK fusionpositive, recurrent, or advanced solid tumors. In August 2019, entrectinib received accelerated approval by the U.

Design, Synthesis and In Vitro Cytotoxic Activity of New 6,9-Disubstituted Purine Analogues.

A series of new 6,9-disubstituted purine analogs with 4-substituted piperazine at C-6 and 4-substituted benzyl at N-9 were designed and synthesized in four steps. All synthesized compounds (7-26) were screened initially for their in vitro anticancer activity on Huh7 liver, HCT116 colon and MCF7 breast carcinoma cell lines. Cytotoxic bioactivity studies revealed that all compounds screened, with compound 19 being the exception, were found to have promising cytotoxic activities at IC50 range of 0.

Highly efficient chemical phosphorylation of 6-(4-phenylpiperazine-1-yl)-9-(β-D-ribofuranosyl)-9-purine.

Antimetabolites, which are metabolic antagonists used in the treatment of cancer and viral diseases by replacing metabolites, inhibit the action of metabolic enzymes and disrupt the pathways of synthesis of structural units necessary for the formation of nucleic acids. Purine antagonists, that are subunits of antimetabolites, reduce the production of purine bases, and hence, cause the nucleotide production to stop and bring about the death of cancer cells. Fludarabine (2-fluoro-ara-AMP), which is used in chemotherapy, is an antimetabolite of the purine class containing mono phosphate in its structure.

Synthesis of novel 6-substituted amino-9-(β-d-ribofuranosyl)purine analogs and their bioactivities on human epithelial cancer cells.

New nucleoside derivatives with nitrogen substitution at the C-6 position were prepared and screened initially for their in vitro anticancer bioactivity against human epithelial cancer cells (liver Huh7, colon HCT116, breast MCF7) by the NCI-sulforhodamine B assay. N-(4-trifluoromethylphenyl)piperazine analog (27) exhibited promising cytotoxic activity. The compound 27 was more cytotoxic (IC = 1-4 μM) than 5-FU, fludarabine on Huh7, HCT116 and MCF7 cell lines.

Synthesis of Some Substituted 6-Phenyl Purine Analogues and Their Biological Evaluation as Cytotoxic Agents.

A series of 6-(4-substituted phenyl)-9-(tetrahydropyran-2-yl)purines 3-9, 6-(4-substituted phenyl)purines 10-16, 9-((4-substituted phenyl)sulfonyl)-6-(4-substituted phenyl)purines 17-32 were prepared and screened initially for their in vitro anticancer activity against selected human cancer cells (liver Huh7, colon HCT116, breast MCF7). 6-(4-Phenoxyphenyl) purine analogues 9, 16, 30-32, had potent cytotoxic activities. The most active purine derivatives 5-9, 14, 16, 18, 28-32 were further screened for their cytotoxic activity in hepatocellular cancer cells.

Synthesis of novel substituted purine derivatives and identification of the cell death mechanism.

Novel 9-(substituted amino/piperazinoethyl)adenines (4-12), 6-(substituted piperazino/amino)purines (15-27), 9-(p-toluenesulfonyl/cyclopentyl/ethoxycarbonylmethyl)-6-(substituted amino/piperazino)purines (28-34, 36, 37, 38-41) were synthesized and evaluated initially for their cytotoxic activities on liver Huh7, breast T47D and colon HCT116 carcinoma cells. N(6)-(4-Trifluoromethylphenyl)piperazine derivative (17) and its 9-(p-toluene-sulfonyl)/9-cyclopentyl analogues (28, 36) had promising cytotoxic activities. Compounds 17, 28 and 36 were further analysed for their cytotoxicity in a panel of a liver cancer cell lines.

Synthesis of novel 6-(4-substituted piperazine-1-yl)-9-(β-D-ribofuranosyl)purine derivatives, which lead to senescence-induced cell death in liver cancer cells.

Novel purine ribonucleoside analogues (9-13) containing a 4-substituted piperazine in the substituent at N(6) were synthesized and evaluated for their cytotoxicity on Huh7, HepG2, FOCUS, Mahlavu liver, MCF7 breast, and HCT116 colon carcinoma cell lines. The purine nucleoside analogues were analyzed initially by an anticancer drug-screening method based on a sulforhodamine B assay. Two nucleoside derivatives with promising cytotoxic activities (11 and 12) were further analyzed on the hepatoma cells.

Synthesis and antimicrobial evaluation of some new substituted purine derivatives.

A series of 8,9-disubstituted adenines (4, 5, 8), 6-substituted aminopurines (10-13) and 9-(p-fluorobenzyl/cyclopentyl)-6-substituted aminopurines (16, 17, 19-30) have been prepared and the antimicrobial activities of these compounds against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA, standard and clinical isolate), Bacillus subtilis, Escherichia coli and Candida albicans were evaluated. 6-[(N-phenylaminoethyl)amino]-9H-purine (12) which has no substitution at N-9 position and 9-cyclopentyl-6-[(4-fluorobenzyl)amino]-9H-purine (24) exhibited excellent activity against C.

Synthesis and in vitro antimicrobial activity of some novel substituted benzimidazole derivatives having potent activity against MRSA.

The novel benzimidazole derivatives (3, 5, 8, 9, 12-14, 18-41) were prepared in this paper and the antimicrobial activities of these compounds against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA, standard and clinical isolates), Bacillus subtilis, Escherichia coli and Candida albicans were evaluated. Compounds 24-26 which have no substitution of N-1 position displayed better antibacterial activities than those of standards (ciprofloxacin, ampicillin and sultamicillin) against both the drug-resistant bacteria (MRSA, standard and clinical isolates).

Synthesis of new 3-(substituted phenacyl)-5-[3'-(4H-4-oxo-1-benzopyran-2-yl)-benzylidene]-2,4-thiazolidinediones and their antimicrobial activity.

Synthesis of 3-(3-nitrophenacyl)thiazolidine-2,4-dione 2g and 3-(substituted phenacyl)-5-[3'-(4H-4-oxo-1-benzopyran-2-yl)-benzylidene]-2,4-thiazolidinediones 4a-g are reported in this paper. These compounds 4a-g were prepared from 3'-flavone carboxaldehyde and 3-substituted phenacyl-2,4-thiazolidinediones using Knoevenagel reaction. The structures of all compounds were confirmed by IR, 1H-NMR, mass spectral data, and elemental analyses.

Antioxidant properties of flavone-6(4')-carboxaldehyde oxime ether derivatives.

The in vitro antioxidant properties of some flavone-6(4)-carboxaldehyde oxime ether derivatives (Ia-f, IIa-f) were determined by their effects on the rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels by measuring the formation of 2-thiobarbituric acid reactive substances. The free radical scavenging properties of the compounds were also examined in vitro by determining their capacity to scavenge superoxide anions and interact with the stable free radical 2, 2-diphenyl-1-picrylhydrazyl (DPPH). The most active compounds, IIb (Flavone-4'-carboxaldehyde-O-ethyl oxime) and Id (Flavone-6-carboxaldehyde-O-[2-(1-pyrolidino) ethyl] oxime), caused 98 and 79% inhibition of superoxide anion production and DPPH stable free radical at 10(-3) M, respectively.

Evaluation of the antioxidant effects of some flavonylthiazolidinediones by determining their effects on lipid peroxidation, superoxide anion formation, and 2,2-diphenyl-1-picrylhydrazyl stable free radical.

The in vitro antioxidant effects of some flavonylthiazolidinediones (Ia-d, IIa-d) on rat liver microsomal NADPH-dependent lipid peroxidation (LP) levels were determined by measuring the formation of 2-thiobarbituric acid reactive substance. The free radical-scavenging properties of the compounds were examined in vitro by determining the capacity to scavenge superoxide anion formation and of the interaction with the stable free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH). The compounds had no inhibitory effects on LP.

5'-nor carbocyclic ribavirin.

An efficient synthesis of 5'-nor carbocyclic ribavirin (4) is described in 13 steps from conveniently available (+)-(IR,4S)-4-hydroxy-2-cyclopenten-1-yl acetate (6). Compound 4 was evaluated against the following viruses: herpes simplex type 1 and 2, vaccinia, cowpox, smallpox, Ebola, hepatitis B, hepatitis C, adenovirus type 1, influenza A (H1N1 and H3N2), influenza B, parainfluenza type 3, Pichinde, Punta Toro A, respiratory syncytial, rhinovirus type 2, Venezuelan equine encephalitis, yellow fever, and West Nile. No activity was found nor was there any cytotoxicity to the viral host cells.

Synthesis and antimicrobial activity of flavone-3'-carboxaldehyde oxime ether derivatives.

A new series of flavonyl oxime ether derivatives (FO1-FO6) was prepared by reaction of flavone-3'-carboxaldehyde (III) with O-substituted hydroxyl amine derivatives (IV). The synthesized compounds were tested for their in vitro antifungal and antibacterial activities. All the compounds exhibited antimicrobial activity.

9-deaza-5'-noraristeromycin.

9-deaza-5'-noraristeromycin (2) has been prepared in 10 steps from the readily available (+)-(1R,4S)-4-t-butyldimethylsilyloxycyclopent-2-en-1-yl acetate. Compound 2 was evaluated against a large number of viruses. No activity was found nor did 2 display cyctotoxicity towards the viral host cells.

Synthesis and hypoglycemic activity of some substituted flavonyl thiazolidinedione derivatives--fifth communication: flavonyl benzyl substituted 2,4-thiazolidinediones.

A new series of 3-benzyl(p-substituted benzyl)-5-[3'-(4H-4-oxo-1-benzopyran-2-yl)-benzylidene]-2,4-thiazolidinediones (8a-e) were synthesized. These products were prepared by Knoevenagel reaction from 3'-flavone carboxaldehyde and 3-substituted 2,4-thiazolidinediones. In vitro insulinotropic activity was determined for compounds 6a-e, 7a-e, 8b and 8c.