5397-78-4

Upstream product

• 2797-51-5 quinoclamine 
• 108-24-7 acetic anhydride 
• 2348-74-5 2-acetylamino-1,4-naphthoquinone 
• 7664-93-9 sulfuric acid 
• 75-36-5 acetyl chloride 
• 15252-69-4 2-chloro-1,4-dihydro-3-methylamino-1,4-dioxonaphthalene 
• 60-35-5 acetamide 
• 117-80-6 2,3-Dichloro-1,4-naphthoquinone 

Downstream Products

• 97339-24-7 5,6-dihydronaphtho<1',2':4,5>imidazo<1,2-a>pyridine-5,6-dione 
• 1526-73-4 3-chloro-2-hydroxy-naphthalene-1,4-dione 
• 13755-96-9 2-acetamido-3-amino-1,4-naphthoquinone 
• 95169-25-8 2-acetamido-3-benzylamino-1,4-naphthoquinone 
• 1429756-60-4 2-N-acteylamino-3-chloro-1,4-naphthoquinone 
• 4572-59-2 1,2-dimethyl-1H-naphtho[2,3-d]imidazole-4,9-dione 
• 93733-07-4 2-methyl-1-propyl-1H-naphtho[2,3-d]imidazole-4,9-dione 
• 32219-31-1 N-[3-(isopropylamino)-1,4-dioxo-1,4-dihydronaphthalen-2-yl]acetamide 

Relevant academic research and scientific papers

Functionalized Dioxonaphthoimidazoliums: A Redox Cycling Chemotype with Potent Bactericidal Activities against Mycobacterium tuberculosis

Disruption of redox homeostasis in mycobacteria causes irreversible stress induction and cell death. Here, we report the dioxonaphthoimidazolium scaffold as a novel redox cycling antituberculosis chemotype with potent bactericidal activity against growing and nutrient-starved phenotypically drug-resistant nongrowing bacteria. Maximal potency was dependent on the activation of the redox cycling quinone by the positively charged scaffold and accessibility to the mycobacterial cell membrane as directed by the lipophilicity and conformational characteristics of the N-substituted side chains. Evidence from microbiological, biochemical, and genetic investigations implicates a redox-driven mode of action that is reliant on the reduction of the quinone by type II NADH dehydrogenase (NDH2) for the generation of bactericidal levels of the reactive oxygen species (ROS). The bactericidal profile of a potent water-soluble analogue 32 revealed good activity against nutrient-starved organisms in the Loebel model of dormancy, low spontaneous resistance mutation frequency, and synergy with isoniazid in the checkerboard assay.

Synthesis and biological activity of imidazole based 1,4-naphthoquinones

Design and development of drugs in multi-drug resistant (MDR) infections have been of growing interest. We report the syntheses, and antibacterial and antifungal activities of imidazole-based 1,4-naphthoquinones (I-1toI-4; 1-alkyl-2-methyl-1H-naphtho[2,3-d]imidazole-4,9-dione (alkyl = methyl to butyl)) and their precursors (B-3;N-(3-chloro-1,-dioxo-1,4-dihydronaphthalen-2-yl)acetamide) andA-1toA-4;N-(3-(alkylamino)-1,4-dioxo-1,4-dihydronaphthalen-2-yl)acetamide (alkyl = methyl to butyl). Crystal structures ofB-3A-1toA-3andI-2toI-4were obtained through single crystal X-ray diffraction experiments. Electronic structure and charge distribution have further been characterized with the use of Density Functional Theory. Seven of these derivatives display a broad spectrum of antibacterial activity against few selected bacterial strains (Gram-positive and Gram-negative). As demonstrated MIC values withB-2andB-3against bacterial isolates were 8-64 μg ml?1and those against pathogenic yeast,C. albicans, were observed in the range of 128-256 μg ml?1. MIC data of these derivatives suggest them to be promising against pathogens.

Antimalarial N1, N3-Dialkyldioxonaphthoimidazoliums: Synthesis, Biological Activity, and Structure-activity Relationships

Here we report the nanomolar potencies of N1,N3-dialkyldioxonaphthoimidazoliums against asexual forms of sensitive and resistant Plasmodium falciparum. Activity was dependent on the presence of the fused quinone-imidazolium entity and lipophilicity imparted by the N1/N3 alkyl residues on the scaffold. Gametocytocidal activity was also detected, with most members active at IC50 1 μM. A representative analog with good solubility, limited PAMPA permeability, and microsomal stability demonstrated oral efficacy on a humanized mouse model of P. falciparum.

Synthesis and biological evaluation of novel 2-arylvinyl-substituted naphtho[2,3-d]imidazolium halide derivatives as potent antitumor agents

Two series of novel 2-arylvinyl-naphtho[2,3-d]imidazol-3-ium iodide derivatives and 2-arylvinyl-naphtho[2,3-d]imidazol-3-ium bromide derivatives were designed and synthesized by the structural combination of YM155 with stilbenoids. All compounds were tested for anti-proliferative activity against PC-3, A375 and HeLa human cancer cell lines. Two of the compounds were selected for further investigation: 12b, which showed potent cytotoxicity against the three tested cell lines with IC50 values in the range of 0.06–0.21 μM, and 7l, which displayed excellent selectivity for PC-3 cells with an IC50 of only 22 nM. Western blot analysis results indicated that both 12b and 7l suppress the expression of Bcl-2 and Survivin proteins, which helps induce apoptosis. As determined by the percent of Annexin V-FITC-positive apoptotic cells, 12b was not only significantly more effective than 7l at a concentration of 100 nM in PC-3 cells but also induced apoptosis in a dose-dependent manner with more potency than 7l at a concentration of 1000 nM in A375 cells. Therefore, compound 12b was chosen for further in-depth studies investigating the mechanism of apoptosis. The results showed that it could activate caspase-3, hydrolyze PARP, and even inactivate ERK. Moreover, 12b arrested A375 cells at S phase in a time-dependent and dose-dependent manner, while having a visible effect on microtubule dynamics. In addition, (E)-2-(2-(1H-indol-3-yl)vinyl)-1-benzyl-3-(2-methoxyethyl)-4,9-dioxo-4,9-dihydro-1H-naphtho[2,3-d]imidazol-3-ium bromide (12b) exhibited significant antitumor activity when evaluated in a subcutaneous solid tumor model. Our study reveals that 2-arylvinyl-substituted naphtho[2,3-d]imidazolium scaffolding is a promising new entity for the development of multi-target anticancer drugs.

A simple synthesis of 3,4-dihydrobenzo[f]quinoxalin-6(2H)-one derivatives substituted in the ring B

[Figure not available: see fulltext.] We followed a simple, inexpensive, and efficient route to synthesize a series of 3,4-dihydrobenzo[f]quinoxalin-6(2H)-one derivatives substituted in the ring B, with the expectation that this scaffold might exhibit antineoplastic activity. 5-Chlorobenzo[f]quinoxalin-6-ylacetate and 4-benzylbenzo[f]quinoxalin-6(4H)-one were obtained for the first time.

COMPOSITIONS AND METHODS FOR TREATMENT OF PROSTATE CARCINOMA

Disclosed herein are 1,4-naphthoquinone analogs, pharmaceutical compositions that include one or more of such 1,4-naphthoquinone analogs, and methods of treating and/or ameliorating diseases and/or conditions associated with a cancer, such as prostate can

Antiproliferative, DNA intercalation and redox cycling activities of dioxonaphtho[2,3-d]imidazolium analogs of YM155: A structure-activity relationship study

The anticancer agent YM155 is widely investigated as a specific survivin suppressant. More recently, YM155 was found to induce DNA damage and this has raised doubts as to whether survivin is its primary target. In an effort to assess the contribution of DNA damage to the anticancer activity of YM155, several analogs were prepared and evaluated for antiproliferative activity on malignant cells, participation in DNA intercalation and free radical generation by redox cycling. The intact positively charged scaffold was found to be essential for antiproliferative activity and intercalation but was less critical for redox cycling where the minimal requirement was a pared down bicyclic quinone. Side chain requirements at the N1 and N3 positions of the scaffold were more alike for redox cycling and intercalation than antiproliferative activity, underscoring yet again, the limited structural overlaps for these activities. Furthermore, antiproliferative activities were poorly correlated to DNA intercalation and redox cycling. Potent antiproliferative activity (IC50 9-23 nM), exceeding that of YM155, was found for a minimally substituted methyl analog AB7. Like YM155 and other dioxonaphthoimidazoliums, AB7 was a modest DNA intercalator but with weak redox cycling activity. Thus, the capacity of this scaffold to inflict direct DNA damage leading to cell death may not be significant and YM155 should not be routinely classified as a DNA damaging agent.

Structure-activity relationships and colorimetric properties of specific probes for the putative cancer biomarker human arylamine N-acetyltransferase 1

A naphthoquinone inhibitor of human arylamine N-acetyltransferase 1 (hNAT1), a potential cancer biomarker and therapeutic target, has been reported which undergoes a distinctive concomitant color change from red to blue upon binding to the enzyme. Here we describe the use of in silico modeling alongside structure-activity relationship studies to advance the hit compound towards a potential probe to quantify hNAT1 levels in tissues. Derivatives with both a fifty-fold higher potency against hNAT1 and a two-fold greater absorption coefficient compared to the initial hit have been synthesized; these compounds retain specificity for hNAT1 and its murine homologue mNat2 over the isoenzyme hNAT2. A relationship between pKa, inhibitor potency and colorimetric properties has also been uncovered. The high potency of representative examples against hNAT1 in ZR-75-1 cell extracts also paves the way for the development of inhibitors with improved intrinsic sensitivity which could enable detection of hNAT1 in tissue samples and potentially act as tools for elucidating the unknown role hNAT1 plays in ER+ breast cancer; this could in turn lead to a therapeutic use for such inhibitors.

Synthesis and characterization of novel unsymmetrical and symmetrical 3-halo- or 3-methoxy-substituted 2-dibenzoylamino-1,4-naphthoquinone derivatives

Symmetrical and unsymmetrical 3-halo- or 3-methoxy- substituted 2-dibenzoylamino- 1,4-naphthoquinone analogs were synthesized with an average yield of 45% via sodium hydride promoted bis-acylation of 2-amino-3-chloro-1,4- naphthoquinone, 2-amino-3-bromo- 1,4-naphthoquinone and 2-amino-3-methoxy-1,4- naphthoquinone.

Synthesis and evaluation of Hsp90 inhibitors that contain the 1,4-naphthoquinone scaffold

High-throughput screening of a library of diverse molecules has identified the 1,4-naphthoquinone scaffold as a new class of Hsp90 inhibitors. The synthesis and evaluation of a rationally-designed series of analogues containing the naphthoquinone core sca