Synthesis and antiproliferative activity of novel 4-substituted-phenoxy-benzamide derivatives

A series of novel 4-substituted-phenoxy-benzamide derivatives bearing an aryl cycloaliphatic amine moiety were synthesized and evaluated for antiproliferative activity against SW620, HT29 and MGC803 cancer cell lines in vitro. The pharmacological data demonstrated that the majority of target compounds exhibitedmoderate efficacy in HT29 and MGC803 cell lines. Compound 10c showed promising inhibition of hedgehog (Hh) signaling pathway in an Hh-related assay. In addition, the superposition pattern of 10c showed a good fit for a pharmacophoric model generated by Hh inhibitors and provided a basis for further structural optimization.     

Synthesis and antiproliferative activity of novel A-homo-B-norsteroid thiadiazole derivatives

Using cholesterol as a starting material, two novel steroidal thiadiazole derivatives possessing a structure of A-homo lactam and a B-nor steroidal skeleton were designed and synthesized by six steps of reactions, and their antiproliferative activities were assayed against various cancer cell lines. The result shows that compound 7b displays an excellent selective inhibition to A-549 (human lung carcinoma) cancer cell lines with an IC₅₀ value of 8.0 μM.     

Synthesis,anti-oxidant activity,and cytotoxicity of salicyloyl derivatives of estra-1,3,5(10)-triene and androst-5-ene

Since many estrane and androstane derivatives exhibit cytotoxic, anti-oxidant, or anti-hormone activity, new steroidal derivatives were synthesised from appropriate estrogen or androgen precursors in order to obtain potential therapeutics for the treatment of steroid-dependent diseases. Starting from estradiol (I), 6-oxo derivatives V and VII were prepared. 17β-Salicyloyl-6-oxo derivatives VI and VIII were synthesised by the reaction of compounds V or VII with methyl salicylate in the presence of sodium. 17β-Salicyloyloxy estradiol IX was prepared from estradiol. Beckmann fragmentation of 16-oxyimino alcohols XII and XIII with methyl salicylate yielded corresponding D-seco derivatives XIV and XV. Simultaneous fragmentation and acylation of compound XII resulted in 3β-salicyloyl-D-seco derivative XVI which was also obtained from compound XIV. Anti-oxidant assays of the newly synthesised compounds V-IX, XIV, and XVI indicated a stronger capacity for hydroxyl radical scavenging, and a weaker capacity for DPPH radical scavenging, compared with the standard anti-oxidants BHA and BHT. Compounds V, XIV, and XVI showed higher or the same activity as BHT. The cytotoxicity of new compounds was evaluated against human breast and prostate carcinoma cells. Compound VI exhibited strong cytotoxicity against MDA-MB-231 cells; compound XIV exhibited strong cytotoxicity against PC-3 cell line, while compound VII moderately inhibited the growth of PC-3 cells.     

Versatile use of hindered oxalates for the stereoselective preparation of novel 11-modified androst-5-ene derivatives

The 11alpha- and 11beta-modified androst-5-ene derivatives 3a,b as well as the exo- and endocyclic dehydrated compounds 4a-c and 5b-c were produced using the oxalate derivatives of the highly hindered 11beta-hydroxyandrost-5-enes 1a-c. The 11-tetrahydrofuran derivative 6 was produced for the first time with good diastereoselectivity by an intramolecular 5-exo cyclization under radical conditions from the corresponding oxalate as precursor.     

Synthesis and in vitro antitumor activity of novel naphthyridinone derivatives

A series of naphthyridinone derivatives based on la(a precursor of Voreloxin) were designed and synthesized.Seven compounds having 70%inhibition against HL60 at 30 μmol/L were further evaluated for their in vitro antitumor activity by SRB assay.Results reveal that thiazol-2-yl and 3-aminomethyl-4-benzyloxyimino-3-methylpyrrolidin-l-yl groups are optimal at the N-1 and C-7positions of naphthyridinone core,respectively.10 j exhibits broad-spectrum activity(IC_(50):0.5-6.25 μmol/L) against all of the tested cell lines including Etoposide- and/or la-resistant ones,and is 1.3-fold to 100-fold more potent than the two references against eight of these cell lines.     

Synthesis and in vitro antitumor activity of novel diaryl urea derivatives

A series of novel diaryl ureas containing 4-[（2-amino-6-trifluromethyl）pyrimidine-4-yl]piperazine-l-yl group were synthesized and evaluated for their cytotoxic activities in a panel of human cancer cell lines. Compared with the reference drug Sorafenib,some compounds showed more potent and a broader spectrum of anti-cancer activities.Among them,compound 2p demonstrated significant inhibitory activities against MDA-MB-231,HT-29 and MCF-7 cell lines with IC₅₀ values of 0.016,0.63,0.001μmol/L, respectively.     

Synthesis of new tetrazolyl derivatives of L- and D-phenylalanine

Russian Journal of Organic Chemistry - New tetrazolyl derivatives of L- and D-phenylalanine were synthesized by azidation of n-propyl esters of (2S)- and...     

Synthesis and evaluation of in vitro anticancer activity of novel solasodine derivatives

<正>Solasodine 11 is a steroidal alkaloid with various biological activities.Herein,8 novel solasodine derivatives were synthesized and their effect on prostate cancer cell proliferation was assessed in vitro.Significant improvement in antiproliferative activity was achieved among some of the synthetic analogs.In particular,19 exhibited the most potent inhibitory effect against the proliferation of PC-3 cell line(IC_(50) = 3.91μmol/L).     

Synthesis and antiproliferative activity of O-silylated nucleoside triazene N-oxide derivatives

A series of modified nucleosides bearing at varied positions of the sugar moiety one 3-aryl-1-triazeno N1-oxide group and a variable number of O-TBDMS groups have been prepared and their cytotoxicities and cytostaticities measured on different cell lines. Nucleosides bearing an aryltriazeno N-oxide group and O-TBDMS groups are either devoid of cytotoxicity or possess a selective cytotoxicity. On the other hand, nucleosides bearing one triazeno group and no silyl group are devoid of cytotoxicity and silylated nucleosides without triazeno group are generally either devoid of cytotoxicity or unselectively cytotoxic. This indicates that the O-TBDMS group per se is not cytotoxic.     

Synthesis and antiproliferative activity of combretastatin derivatives with adamantane fragment

Russian Chemical Bulletin - The work describes the synthesis of 2-adamantyl 7-[(2-{[(2E)-3-(3-hydroxy-4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)prop-2-enoyl]amino}ethyl)amino]-7-oxoheptanoate and...     

Synthesis of novel type pyrazolyl and tetrazolyl isoquinolinium zwitterions

New type pyrazol‐3‐yl‐isoquinolinium hydrochloride ( 8a ) and tetrazol‐5‐yl‐isoquinolinium ( 8b ) zwitterions were synthesised. Their structures were proved by ir, pmr, cmr, ms spectra as well as X‐ray diffraction analysis of model compounds.     

Synthesis,antiproliferative activity and docking study of novel rhodanine derivatives as Bcr-Abl T1351 inhibitors

Research on Chemical Intermediates - A series of novel N-substituted rhodanines 6a–g were synthesized by a microwave synthesizer, and evaluated for their anti-proliferative activity. Most of...     

Synthesis of novel 2,4,6-trisubstituted pyrimidine derivatives and their in vitro antimicrobial activity

A series of novel pyrimidines (6a–6i) has been synthesized from corresponding chalcones and isonicotinimidamide.HCl in the presence of potassium carbonate involving Michael addition followed by cycloaddition. All newly synthesised chalcones and pyrimidines were screened for in vitro antimicrobial activity against various Gram positive, Gram negative bacterial and fungal strains. Most of compounds displayed high antimicrobial activity compared to standard drugs Penicillin, Streptomycin and Ampothericin-B.     

Synthesis,antifungal activity and in vitro mechanism of novel 1-substituted-5-trifluoromethyl-1H-pyrazole-4-carboxamide derivatives

Inspired by the wide application of amides in plant pathogens, a series of novel 1-substituted-5-trifluoromethyl?1H?pyrazole-4-carboxamide derivatives were designed and synthesized. Bioassay results indicated that some target compounds exhibited excellent and broad-spectrum in vitro and certain in vivo antifungal activities. Among them, the in vitro EC₅₀ values of Y₁₃ against G. zeae, B. dothidea, F. prolifeatum and F. oxysporum were 13.1, 14.4, 13.3 and 21.4 mg/L, respectively. The in vivo protective activity of Y₁₃ against G. zeae at 100 mg/L was 50.65%. SAR analysis revealed that the phenyl on the 1-position of the pyrazole ring was important for this activity. An antifungal mechanism study of Y₁₃ against G. zeae demonstrated that this compound may disrupt the cell membrane of mycelium, thus inhibiting the growth of fungi. These mechanistic study results were inconsistent with those for traditional amides and may provide a novel view for deep study of this series of pyrazole carboxamide derivatives.     

Synthesis, DNA-binding and antiproliferative properties of acridine and 5-methylacridine derivatives

Several acridine derivatives were synthesized and their anti-proliferative activity was determined. The most active molecules were derivatives of 5-methylacridine-4-carboxylic acid. The DNA binding properties of the synthesized acridines were analyzed by competitive dialysis and compared with the anti-proliferative activities. While inactive acridine derivatives showed high selectivity for G-quadruplex structures, the most active 5-methylacridine-4-carboxamide derivatives had high affinity for DNA but showed poor specificity. An NMR titration study was performed with the most active 5-methylacridine-4-carboxamide, confirming the high affinity of this compound for both duplex and quadruplex DNAs.     

In vitro antiproliferative activity of glabridin derivatives and their in silico target identification

Abstract

Novel Mannich base derivatives of glabridin were synthesized and their antiproliferative activity were performed along with our previously reported glabridin-chalcone hybrids molecules (GCHMs) against various human cell lines MDA-MB-231 (breast adenocarcinoma), HEK-293 (embryonic kidney cell line), K562 (leukemia), MCF-7 (breast adenocarcinoma), HeLa (cervix adenocarcinoma), HepG2 (hepatocellular carcinoma) and WRL-68 (hepatic carcinoma). The result showed that the glabridin significantly reduced cell proliferation with IC₅₀ ranges from 3.67 to 58.30?µM against all the tested cell lines. The remarkable reduction in antiproliferative activity 2’,4’-dimethoxyglabridin and GCHMs compounds with phenolic OH groups protected by methoxy (OCH₃) groups suggested that the free OH groups are essential factor for the antiproliferative activity of glabridin and its derivatives. The Mannich base derivatives of glabridin showed moderate activity IC₅₀ (2.20–>95.78?µM). Furthermore, in silico target identification analysis revealed that AKT1, DECR1 and NOS1 are the potential targets for glabridin and their derivatives.     

Synthesis,characterization and in vitro antimicrobial activity of some novel 5-substituted Schiff and Mannich base of isatin derivatives

With the aim of developing potential antimicrobials, a series of novel Ciprofloxacin methylene isatin derivatives incorporating different aromatic aldehydes were synthesized and characterized by FTIR, ¹H NMR, Mass spectroscopy and bases of elemental analysis. In addition, the in vitro antibacterial and antifungal properties were tested against some human pathogenic microorganisms by employing the disc diffusion technique. A majority of compounds were showing activity against several of the microorganisms. The relationship between the functional group variation and the biological activity of the evaluated compounds is discussed. From comparisons of the compounds, 3c was determined to be the most active compound.     

Synthesis and biological activity of novel 2-methyl-4-trifluoromethyl-thiazole-5-carboxamide derivatives

Nine novel 2-methyl-4-trifluoromethylthiazole-5-carboxamide derivatives were designed and synthesized utilizing ethyl 4,4,4-trifluoroacetoacetate as a starting material. Subsequently, the biological activity of the compounds was evaluated in the greenhouse. Results indicated that all of the compounds have some fungicidal and insecticidal activity but no herbicidal activity. Compound 1 has fungicidal activity with 90% control of tomato late blight at 375 g ai/ha, while two compounds 2F and 2H show insecticidal activity with 80 and 100% control, respectively, against potato leafhopper at 600 g ai/ha.