Synthesis of radiolabeled biphenylsulfonamide matrix metalloproteinase inhibitors as new potential PET cancer imaging agents

Novel matrix metalloproteinase (MMP) inhibitor radiotracers, (S)-3-methyl-2-(2',3',4'-methoxybiphenyl-4-sulfonylamino)-butyric acid [(11)C]methyl ester (1a-c), (S)-3-methyl-2-(2',3',4'-fluorobiphenyl-4-sulfonylamino)-butyric acid [(11)C]methyl ester (1d-f), and (S)-3-methyl-2-(4'-nitrobiphenyl-4-sulfonylamino)-butyric acid [(11)C]methyl ester (1g), a series of substituted biphenylsulfonamide derivatives, have been synthesized for evaluation as new potential positron emission tomography (PET) cancer imaging agents.     

Synthesis of N6-substituted 9-[3-(phosphonomethoxy)propyl]adenine derivatives as possible antiviral agents

A number of N6-substituted 9-[3-(phosphonomethoxy)propyl]adenine derivatives having hydroxymethyl at C-1' position were prepared from the appropriate 6-chloroadenine derivative. The syntheses of the corresponding prodrugs of these compounds are also reported. These compounds showed poor activity against HCV in replicon assay.     

Synthesis of chalcone derivatives on steroidal framework and their anticancer activities

Chalcone derivatives on estradiol framework have been synthesized. Some of the derivatives showed potent anticancer activity against some human cancer cell lines. Compounds 9 and 19 showed potent activity against MCF-7, a hormone dependent breast cancer cell line. Chalcone 7 was further modified to the corresponding indanone derivative (19) using the Nazarov reaction, which showed better activity than the parent compound against the MCF-7 breast cancer cell line. Active anticancer derivatives were also evaluated for osmotic hemolysis using the erythrocyte as a model system. It was observed that chalcone derivatives showing cytotoxicity against cancer cell lines did not affect the fragility of erythrocytes and hence may be considered as non-toxic to normal cells.     

Synthesis and antibacterial activity of the new 9-aminoacridine, 10,11-dihydro-5H-dibenzo[b,f]azepine, polyfluoro 5,6-dihydro-1,3,5-oxadiazine derivatives]

Screening among 9-aminoacridine, 10,11-dihydro-5H-dibenz[b, f]azepine and polyfluoro 5,6-dihydro-1,3,5-oxadiazine derivatives allowed to isolate compounds with potential antibacterial activity. Schemes of the active compounds synthesis are given. The most important is the estimation of the oxydiazines activity against gram-positive microorganisms including methicillin-resistant staphylococci. Special attention is paid to the activity of iminodibenzyl derivatives against multiresistant gram-negative microorganisms.     

9-Deoxopodophyllotoxin derivatives as anti-cancer agents.

Several 9-deoxo-9-substituted podophyllotoxin derivatives were synthesised starting from naturally occuring podophyllotoxin and their anti-cancer activity was evaluated against in vitro human cancer cell line assay. It was observed that these compounds do possess good anti-cancer activity particularly against ovarian, renal and lung cancer cell lines.     

Novel naphthoquinone derivatives: Synthesis and activity against human African trypanosomiasis

A series of naphthoquinone derivatives has been synthesized and tested for its biological activity against human African trypanosomiasis. The use of reverse micellar medium not only enhanced the conversion rate, but also showed selectivity towards mono-coupled product in aryl chloride–aniline coupling reactions. Two derivatives of naphthoquinone (9b and 9c) exhibited potent activity against Trypanosoma brucei in vitro with low cytotoxicity.     

Neo-tanshinlactone inspired synthesis, in vitro evaluation of novel substituted benzocoumarin derivatives as potent anti-breast cancer agents

A small library of novel benzocoumarin derivatives based on naturally occurring neo-tanshinlactone scaffold was constructed and their antiproliferative activities against breast cancer cells MCF-7 and MDA-MB-231 were evaluated. A number of derivatives showed good anti-breast cancer activity, in some cases higher to that of the reference compound tamoxifen. In particular, benzocoumarins Bc-5, Bc-8 and Bc-9 strongly inhibited the proliferation of MCF-7 cancer cell line with the IC(50) values of 3.8, 7.9 and 6.5 μM, respectively. The compounds were capable of inducing nuclear fragmentation, cell cycle arrest and caspase dependent apoptosis in MCF-7 cell lines. In addition, these derivatives were devoid of cytotoxic effect against normal osteoblast cells. These synthetic benzocoumarins hold promises for developing safer alternative to the existing anti-breast cancer agents.     

Synthesis and biological evaluation of 9-substituted tetracycline derivatives

The synthesis of 9-substituted tetracycline derivatives has been accomplished by the reaction of C9 diazonium tetrafluoroborate tetracycline salts with organotin reagents under modified Stille coupling conditions. Several of these unreported derivatives show promising in vitro biological activity against tetracycline resistant and antibiotic resistant bacteria.     

Oxal hydroxamic acid derivatives with inhibitory activity against matrix metalloproteinases

Several amines, amino acid derivatives and low molecular weight peptides containing an amide-bound oxal hydroxamic acid moiety have been synthesized and tested for their inhibitory effects towards native human gelatinase B (MMP-9) and the catalytic domains of the membrane type MT1-MMP (MMP-14) and of neutrophil collagenase (MMP-8). A number of these compounds exhibited considerable inhibitory activity against the tested metalloproteinases.     

Design and synthesis of new 7-(N-substituted-methyl)-camptothecin derivatives as potent cytotoxic agents

A series of novel 7-(N-substituted-methyl)-camptothecin derivatives was designed, synthesized, and evaluated for in vitro cytotoxicity against four human tumor cell lines, A-549, MDA-MB-231, KB, and KBvin. All of the derivatives showed promising in vitro cytotoxic activity against the tested tumor cell lines, with IC₅₀ values ranging from 0.0023 to 1.11 μM, and were as or more potent than topotecan. Compounds 9d, 9e, and 9r exhibited the highest antiproliferative activity among all prepared derivatives. Furthermore, all of the compounds were more potent than paclitaxel against the multidrug-resistant (MDR) KBvin subline. With a concise efficient synthesis and potent cytotoxic profiles, especially significant activity towards KBvin, compounds 9d, 9e, and 9r merit further development as a new generation of camptothecin-derived anticancer clinical trial candidates.     

Synthesis of tetrocarcin derivatives with specific inhibitory activity towards Bcl-2 functions

Tetrocarcin A was recently identified as an inhibitor of the anti-apoptotic function of Bcl-2. We synthesized novel tetrocarcin derivatives in order to increase their selective inhibitory activity against Bcl-2. It was found that 21-acetoxy-9-glycosyloxy derivatives had potent Bcl-2 inhibitory activity without significant antimicrobial activity.     

Syntheses of novel antitumor dihydroxanthone derivatives with inhibitory activity against DNA topoisomerase II.

A series of methoxycarbonyl group modified nidulalin A analogs were synthesized to improve stability against esterases. The amide derivatives showed cytotoxic activity along with inhibitory activity against DNA topoisomerase II. Among the analogs, amide 9a exhibited antitumor activity in Colon 26 murine tumor model.     

Synthesis of new sulfonamides as lipoxygenase inhibitors

The present study describes a convenient method for the synthesis of new lipoxygenase inhibitors, 4-(toluene-4-sulfonylamino)-benzoic acids from p-amino benzoic acid. Reaction of p-amino benzoic acid with p-toluenesulfonyl chloride provided thirteen N- and O-alkylation products 4a-4m in moderate to good yields. Lipoxygenase inhibition of newly formed sulfonamide derivatives was investigated and some of these compounds 4m, 4g, 4e, 4f and 4j showed good lipoxygenase inhibitory activities with IC(50) values ranged between 15.8 ± 0.57 and 91.7 ± 0.61 μmol whilst all other compounds exhibited mild anti-lipoxygenase activities with IC(50) values ranged between 139.2 ± 0.75 and 232.1 ± 0.78 μmol. N-alkylated products were more active against the enzyme than O-alkylated or both N- and O-alkylated ones. All synthesized sulfonamides were recrystallized in chloroform to give these title compounds which were characterized using FTIR, (1)H NMR, (13)C NMR, elemental analysis and single crystal X-ray diffraction techniques.     

Synthesis of purine bases having a di(hydroxymethyl)cyclopentenyl group by means of high-pressure reaction and their anti-HIV activity.

The 1'- and 5'-hydroxymethyl derivatives of carbovir and related purine derivatives were synthesized from 5-hydroxymethylcyclopentadiene. The anti-HIV activity evaluation of these compounds has revealed that 9-(c-4,t-5-dihydroxymethylcyclopent-2-en-r-1-yl)-9H-adenine is a prospective chemotherapeutic agent against AIDS.     

Design, synthesis and activity against human cytomegalovirus of non-phosphorylatable analogs of toyocamycin, sangivamycin and thiosangivamycin

A number of 7-alkyl 4-aminopyrrolo[2,3- pyrimidine derivatives related to toyocamycin, sangivamycin and thiosangivamycin have been prepared and tested for their activity against human cytomegalovirus (HCMV). Only the thioamide substituted derivatives demonstrated biological activity.     

Muraymycins,novel peptidoglycan biosynthesis inhibitors: semisynthesis and SAR of their derivatives

Sixteen muraymycin derivatives 2-17 were synthesized based on selective reactions of the primary and secondary amino groups of muraymycin C1 (1) with isocyanates and aldehydes. Disubstituted derivatives 3-9 demonstrated no activity against either MraY or MurG at 相似文献   

Antimalarial activity of 3-hydroxyalkyl-2-methylene-propionic acid derivatives

Several Baylis-Hillman adducts and their derivatives were synthesized and evaluated as targeted potential anti-malarials. The compounds 4, 7 and 9 were found to have highest potency against P. falciparum in vitro. The in vivo test result of compound 4 and 9 against P. berghei demonstrated activity at 80 mg/Kg dose level.     

Synthesis of N6-Substituted 9-[3-(Phosphonomethoxy)Propyl]Adenine Derivatives As Possible Antiviral Agents

A number of N ⁶ -substituted 9-[3-(phosphonomethoxy)propyl]adenine derivatives having hydroxymethyl at C-1′-position were prepared from the appropriate 6-chloroadenine derivative. The syntheses of the corresponding prodrugs of these compounds are also reported. These compounds showed poor activity against HCV in replicon assay.     

Synthesis and antibacterial activity of N-[2-[5-(methylthio)thiophen-2-yl]-2-oxoethyl] and N-[2-[5-(methylthio)thiophen-2-yl]-2-(oxyimino)ethyl]piperazinylquinolone derivatives

A number of N-substituted piperazinylquinolone derivatives were synthesized and evaluated for antibacterial activity against Gram-positive and Gram-negative bacteria. Preliminary results indicated that most compounds tested in this study demonstrated comparable or better activity against Staphylococcus aureus and Staphylococcus epidermidis than their parent piperazinylquinolones as reference drugs. Among these derivatives, ciprofloxacin derivative 5a, containing N-[2-[5-(methylthio)thiophen-2-yl]-2-oxoethyl] residue, showed significant improvement of potency against staphylococci, maintaining Gram-negative coverage.     

Growth inhibition activity of thioacetal artemisinin derivatives against human umbilical vein endothelial cells

Thioacetal artemisinin derivatives, in particular, 10alpha-phenylthiodihydroartemisinins (5), 10beta-benzenesulfonyl-9-epi-dihydroartemisinin (9) and 10alpha-mercaptodihydroartemisinin (11), exhibit good growth inhibition activity against HUVEC proliferation at the concentration level of 1 microM.