- Novel benzimidazolyl tetrahydroprotoberberines: Design, synthesis, antimicrobial evaluation and multi-targeting exploration
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A series of novel benzimidazolyl tetrahydroprotoberberines were conveniently designed and efficiently synthesized from berberine via direct cyclization of tetrahydroprotoberberine aldehyde and o-phenylene diamines under metal-free aerobic oxidation. All the new compounds were characterized by IR, 1H NMR, 13C NMR and HRMS spectra. The antimicrobial evaluation revealed that the 5-fluorobenzimidazolyl derivative 5b was the most active antibacterial and antifungal molecule with broad spectrum in comparison to Berberine, Chloromycin, Norfloxacin and Fluconazole. It triggered almost no resistance development against MRSA even after 15 passages. Further studies demonstrated that compound 5b could not only effectively interact with Topo IA by hydrogen bonds, but also intercalate into calf thymus DNA and cleave pBR322 DNA, which might be responsible for its powerful bioactivities.
- Jeyakkumar, Ponmani,Liu, Han-Bo,Gopala, Lavanya,Cheng, Yu,Peng, Xin-Mei,Geng, Rong-Xia,Zhou, Cheng-He
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- Supramolecular Chemistry-Based One-Pot High-Efficiency Separation of Solubilizer-Free Pure Semiconducting Single-Walled Carbon Nanotubes: Molecular Strategy and Mechanism
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Single-walled carbon nanotubes (SWCNTs) have the potential to revolutionize nanoscale electronics and power sources; however, their low purity and high separation cost limit their use in practical applications. Here we present a supramolecular chemistry-based one-pot, less expensive, scalable, and highly efficient separation of a solubilizer/adsorbent-free pure semiconducting SWCNT (sc-SWCNT) using flavin/isoalloxazine analogues with different substituents. On the basis of both experimental and computational simulations (DFT study), we have revealed the molecular requirements of the solubilizers as well as provided a possible mechanism for such a highly efficient selective sc-SWCNT separation. The present sorting method is very simple (one-pot) and gives a promising sc-SWCNT separation methodology. Thus, the study provides insight for the molecular design of an sc-SWCNT solubilizer with a high (n,m)-chiral selectivity, which benefits many areas including semiconducting nanoelectronics, thermoelectric, bio and energy materials, and devices using solubilizer-free very pure sc-SWCNTs.
- Nakashima, Naotoshi,Fukuzawa, Masashi,Nishimura, Kanako,Fujigaya, Tsuyohiko,Kato, Yuichi,Staykov, Aleksandar
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- Novel purine benzimidazoles as antimicrobial agents by regulating ROS generation and targeting clinically resistant Staphylococcus aureus DNA groove
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A novel series of purine benzimidazole hybrids were designed and synthesized for the first time with the aim to circumvent the increasing antibiotic resistance. Hexyl appended hybrid 3c gave potent activities against most of the tested bacteria and fungi especially against multidrug-resistant strains Staphylococcus aureus (MIC = 4 μg/mL). Structure-activity relationships revealed that the benzimidazole fragment at the 9-position of purine played an important role in exerting potentially antibacterial activity. Both cell toxicity and ROS generation assays indicated that the purine derivative 3c showed low cytotoxicity and could be used as a safe agent. Molecular modeling suggested that hybrid 3c could bind with the residues of Topo IA through hydrogen bonds and electrostatic interactions. Quantum chemical studies were also performed on the target compound 3c to understand the structural features essential for activity. The active molecule 3c could effectively interact with S. aureus DNA to form 3c–DNA complex through groove binding mode, which might block DNA replication to display their powerful antimicrobial activity.
- Wang, Ya-Nan,Bheemanaboina, Rammohan R. Yadav,Cai, Gui-Xin,Zhou, Cheng-He
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supporting information
p. 1621 - 1628
(2018/03/29)
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- Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug-Resistant Pseudomonas aeruginosa DNA
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A series of benzimidazole–quinolone hybrids as new potential antimicrobial agents were designed and synthesized. Bioactive assays indicated that some of the prepared compounds exhibited potent antibacterial and antifungal activities. Notably, 2-fluorobenzyl derivative 5 b (ethyl 7-chloro-6-fluoro-1-[[1-[(2-fluorophenyl)methyl]benzimidazol-2-yl]methyl]-4-oxo-quinoline-3-carboxylate) showed remarkable antimicrobial activity against resistant Pseudomonas aeruginosa and Candida tropicalis isolated from infected patients. Active molecule 5 b could not only rapidly kill the tested strains, but also exhibit low toxicity toward Hep-2 cells. It was more difficult to trigger the development of bacterial resistance of P. aeruginosa against 5 b than that against norfloxacin. Molecular docking demonstrated that 5 b could effectively bind with topoisomerase IV–DNA complexes, and quantum chemical studies theoretically elucidated the good antimicrobial activity of compound 5 b. Preliminary experimental reaction mechanism exploration suggested that derivative 5 b could not intercalate into DNA isolated from drug-resistant P. aeruginosa, but was able to cleave DNA effectively, which might further block DNA replication to exert powerful bioactivities. In addition, compound 5 b is a promising antibacterial agent with membrane disruption abilities.
- Wang, Ya-Nan,Bheemanaboina, Rammohan R. Yadav,Gao, Wei-Wei,Kang, Jie,Cai, Gui-Xin,Zhou, Cheng-He
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p. 1004 - 1017
(2018/04/30)
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- Design, synthesis and biological evaluation of 5-fluorouracil-derived benzimidazoles as novel type of potential antimicrobial agents
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A series of 5-fluorouracil benzimidazoles as novel type of potential antimicrobial agents were designed and synthesized for the first time. Bioactive assay manifested that some of the prepared compounds exhibited good or even stronger antibacterial and an
- Fang, Xue-Jie,Jeyakkumar, Ponmani,Avula, Srinivasa Rao,Zhou, Qian,Zhou, Cheng-He
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p. 2584 - 2588
(2016/05/09)
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- Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents
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A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 μM concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m-DNA complex which might further block DNA replication to exert the powerful bioactivities.
- Zhang, Ling,Addla, Dinesh,Ponmani, Jeyakkumar,Wang, Ao,Xie, Dan,Wang, Ya-Nan,Zhang, Shao-Lin,Geng, Rong-Xia,Cai, Gui-Xin,Zhou, Cheng-He,Li, Shuo
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p. 160 - 182
(2018/05/17)
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- O- and N-Alkylsubstituted 2-(2'-Hydroxyphenyl)-benzimidazoles and -1,3,4-Oxadiazoles as Complexing and Extracting Agents for Copper-II-Ions
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2-(2'-Alkoxyphenyl)-benzimidazoles 1, 1-alkyl-2-(2'-hydroxyphenyl)-benzimidazoles 2, 2-(2'-hydroxy-4'-alkoxyphenyl)-benzimidazoles 3, 2-(2',4'-dialkoxyphenyl)-benzimidazoles 4 and 1-alkyl-2-(2'-hydroxy-5'-nitrophenyl)-benzimidazoles 7 are synthesized by condensation of 2-hydroxybenzoic acid derivatives and o-phenylendiamine or its derivatives.Alkyl chains (C4, C8 or C12) are introduced by alkylation before or after the ring closure in order to increase the solubility of the reagent in toluene or n-octane.Furthermore the extraction properties of the benzimidazoles are investigated.Also some new analogous compounds of the benzothiazole and the 1,3,4-oxadiazole series were synthesized.
- Beger, J.,Wagner, G.,Uhlig, E.,Dinjus, U.
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p. 708 - 718
(2007/10/02)
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- COENZYME MODELS. PART 29. ON THE UNUSUAL SPECTROSCOPIC BEHAVIOUR OF 10-DODECYL-3-METHYLISOALLOXAZINE (AMPHIPHILIC FLAVIN ANALOGUE) IN AQUEOUS SOLUTION.
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At room temperature in aqueous solution, the visible absorption peak (S1) of the title isoalloxazine (3) gave a well resolved, three-band fine structure which is believed to appear only in apolar solvents or in enzymatic hydrophobic pockets where isoallox
- Shinkai, Seiji,Harada, Akiko,Ishikawa, Yu-ichi,Manabe, Osamu
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p. 125 - 134
(2007/10/02)
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- Alkyl 4-(o-aminophenyl)-3-thioallophanates
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Various alkyl 4-(o-aminophenyl)-3-thioallophanates and alkyl 4-(o-alkylaminophenyl)-3-thioallophanates are useful as fungicides and mite ovicides. The compounds are prepared by reacting an o-phenylenediamine with the appropriate alkoxycarbonylisothiocyanate and an exemplary species is methyl 4-(o-aminophenyl)-3-thioallophanate.
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