Synthesis and biological evaluation of benzimidazole-5-carbohydrazide derivatives as antimalarial, cytotoxic and antitubercular agents.

Abstract:

:A series of N'-substituted-2-(5-nitrofuran or 5-nitrothiophen-2-yl)-3H-benzo[d]imidazole-5-carbohydrazide derivatives were synthesized and investigated for their abilities to inhibit β-hematin formation, hemoglobin hydrolysis and in vivo for their antimalarial efficacy in rodent Plasmodium berghei. Selected analogues were screened for their antitubercular activity against sensitive MTB H(37)Rv and multidrug-resistant MDR-MTB strains, and cytotoxic activity against a panel of human tumor cell lines and two nontumourogenic cell lines. Compounds 3a, 5a, f, 6g were the most promising as inhibitors of β-hematin formation, however, their effect as inhibitors of hemoglobin hydrolysis were marginal. The most active compounds to emerge from the in vitro and in vivo murine studies were 3a and 6i, suggesting an antimalarial activity via inhibition of β-hematin formation and are as efficient as chloroquine. The cytotoxic and antitubercular activities of the present compounds were not comparable with those of the standard drugs employed. But, however, compound 5b showed better antitubercular activity compared to rifampin against multidrug-resistant MDR-MTB strains. Compounds 3a, 6i and 5b showed a good safety index.

journal_name

Bioorg Med Chem

authors

Camacho J,Barazarte A,Gamboa N,Rodrigues J,Rojas R,Vaisberg A,Gilman R,Charris J

doi

10.1016/j.bmc.2011.01.050

subject

Has Abstract

pub_date

2011-03-15 00:00:00

pages

2023-9

issue

6

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(11)00079-4

journal_volume

19

pub_type

杂志文章
  • Design, synthesis and preliminary biological evaluation of indoline-2,3-dione derivatives as novel HDAC inhibitors.

    abstract::Histone deacetylases (HDACs) are zinc-dependent or NAD(+) dependent enzymes and play a critical role in the process of tumor development. Herein a series of indoline-2,3-dione derivatives have been designed and synthesized as potential HDACs inhibitors. The preliminary biological evaluation showed that most compounds ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.05.048

    authors: Jin K,Li S,Li X,Zhang J,Xu W,Li X

    更新日期:2015-08-01 00:00:00

  • Antiproliferative and apoptosis-inducing activities of novel naphthalimide-cyclam conjugates through dual topoisomerase (topo) I/II inhibition.

    abstract::A novel series of naphthalimide-cyclam conjugates were designed and synthesized. Among them, compounds 4c, 4d, 8c and 8d which bearing long lipophilic alkyl chains, displayed comparable or more potent cytotoxic activities against human tumor cell lines than amonafide. Furthermore, the four compounds were proved to pos...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.07.011

    authors: Tan S,Sun D,Lyu J,Sun X,Wu F,Li Q,Yang Y,Liu J,Wang X,Chen Z,Li H,Qian X,Xu Y

    更新日期:2015-09-01 00:00:00

  • Antifungal polyketide derivatives from the endophytic fungus Aplosporella javeedii.

    abstract::Six new polyketides aplojaveediins A-F (1-6) were isolated from the endophytic fungus Aplosporella javeedii associated with the host plant Orychophragmus violaceus (Brassicaceae). The structures of the new metabolites were elucidated by analysis of their NMR and MS data. Compound 1 exhibited antifungal activity agains...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115456

    authors: Gao Y,Wang L,Kalscheuer R,Liu Z,Proksch P

    更新日期:2020-05-15 00:00:00

  • N-aroyloxylthioxo-naphthalimides as DNA photocleavers of aroyloxyl oxygen radicals: synthesis, evaluation, and substituents' effect.

    abstract::Novel N-Aroyloxylthioxo-naphthalimides as highly efficient 'time-resolved' DNA photocleavers of aroyloxyl radicals type were designed and synthesized. The substituents at the aroyloxyl moiety have an important and unusual influence on the DNA photocleavage, and DNA photodamages of the compounds were unusually not depe...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.02.013

    authors: Xu Y,Huang X,Qian X,Yao W

    更新日期:2004-05-01 00:00:00

  • 2-O-substituted cyclodextrins as reversal agents for the neuromuscular blocker rocuronium bromide.

    abstract::A series of secondary face modified cyclodextrins (CDs) were synthesised with the aim of constructing host molecules capable of forming host-guest complexes with neuromuscular blockers, especially with rocuronium bromide. Perfacial 2-O-substitution of gamma-CD with 4-carboxybenzyl resulted in a CD host molecule 1 that...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(02)00026-3

    authors: Tarver GJ,Grove SJ,Buchanan K,Bom A,Cooke A,Rutherford SJ,Zhang MQ

    更新日期:2002-06-01 00:00:00

  • Alkyl deoxy-arabino-hexopyranosides: synthesis, surface properties, and biological activities.

    abstract::Octyl and dodecyl glycosides possessing 2-deoxy-arabino-hexopyranoside moieties belonging to the D- and L-series in their alpha- and beta-forms were synthesized by reaction of an acetyl protected glycal with octanol or dodecanol, catalyzed by triphenylphosphine hydrobromide, followed by deprotection. Their surface pro...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2008.01.020

    authors: Silva FV,Goulart M,Justino J,Neves A,Santos F,Caio J,Lucas S,Newton A,Sacoto D,Barbosa E,Santos MS,Rauter AP

    更新日期:2008-04-01 00:00:00

  • Drug design and synthesis of epsilon opioid receptor agonist: 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821) inducing antinociception mediated by putative epsilon opioid

    abstract::Here we report the new drug design and synthesis of a series of 6,14-endoethenomorphinan-7-carboxamide derivatives as a putative epsilon opioid receptor agonist. One of these compounds, 17-(cyclopropylmethyl)-4,5alpha-epoxy-3,6beta-dihydroxy-6,14-endoethenomorphinan-7alpha-(N-methyl-N-phenethyl)carboxamide (TAN-821), ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.05.024

    authors: Fujii H,Narita M,Mizoguchi H,Murachi M,Tanaka T,Kawai K,Tseng LF,Nagase H

    更新日期:2004-08-01 00:00:00

  • Anti-tubercular activities of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine analogues endowed with high activity toward non-replicative Mycobacterium tuberculosis.

    abstract::Thirty three derivatives of 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine analogues were synthesized by molecular modification of a reported antimycobacterial molecule (GSK163574A). Compounds were evaluated in vitro against actively replicative and nutrient starved non-replicative Mycobacter...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.09.012

    authors: Samala G,Brindha Devi P,Saxena S,Gunda S,Yogeeswari P,Sriram D

    更新日期:2016-11-01 00:00:00

  • Synthesis, antiproliferative and pro-apoptotic activity of 2-phenylindoles.

    abstract::Breast cancer is the second most common cancer worldwide after lung cancer with the vast majority of early stage breast cancers being hormone-dependent. One of the major therapeutic advances in the clinical treatment of breast cancer has been the introduction of selective estrogen receptor modulators (SERMs). We descr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.06.050

    authors: Kelly PM,Bright SA,Fayne D,Pollock JK,Zisterer DM,Williams DC,Meegan MJ

    更新日期:2016-09-15 00:00:00

  • Synthesis and initial PET imaging of new potential dopamine D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides.

    abstract::D3 receptor radioligands (E)-4,3,2-[11C]methoxy-N-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl-cinnamoylamides (4-[11C]MMC, [11C]1a; 3-[11C]MMC, [11C]1b; and 2-[11C]MMC, [11C]1c) were synthesized for evaluation as novel potential positron emission tomography (PET) imaging agents for brain D3 receptors. The new tracers 4...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2005.06.055

    authors: Gao M,Mock BH,Hutchins GD,Zheng QH

    更新日期:2005-11-15 00:00:00

  • Synthesis and characterization of a small analogue of the anticancer natural product leinamycin.

    abstract::Leinamycin (1) is a Streptomyces-derived natural product that displays nanomolar IC(50) values against human cancer cell lines. In the work described here, we report the synthesis and characterization of a small leinamycin analogue 19 that closely resembles the 'upper-right quadrant' of the natural product, consisting...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.10.021

    authors: Keerthi K,Rajapakse A,Sun D,Gates KS

    更新日期:2013-01-01 00:00:00

  • Activation of lysine-specific demethylase 1 inhibitor peptide by redox-controlled cleavage of a traceless linker.

    abstract::We have previously employed cyclization of a linear peptide as a strategy to modulate peptide function and properties, but cleavage to regenerate the linear peptide left parts of the linker structure on the peptide, interfering with its activity. Here, we focused on cyclization of a linear peptide via a "traceless" di...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2016.12.033

    authors: Amano Y,Umezawa N,Sato S,Watanabe H,Umehara T,Higuchi T

    更新日期:2017-02-01 00:00:00

  • Design, synthesis and anti-inflammatory activity of imidazol-5-yl pyridine derivatives as p38α/MAPK14 inhibitor.

    abstract::P38α/MAPK14 is intracellular signalling regulator involved in biosynthesis of inflammatory mediator cytokines (TNF-α, IL-1, IL-6, and IL-1b), which induce the production of inflammatory proteins (iNOS, NF-kB, and COX-2). In this study, drug repurposing strategies were followed to repositioning of a series of B-RAF V60...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115969

    authors: Ali EMH,Abdel-Maksoud MS,Hassan RM,Mersal KI,Ammar UM,Se-In C,He-Soo H,Kim HK,Lee A,Lee KT,Oh CH

    更新日期:2021-02-01 00:00:00

  • The adduct formation between the thioguanine-polyamine ligands and DNA with the AP site under UVA irradiated and non-irradiated conditions.

    abstract::The AP sites are representative of DNA damage and known as an intermediate in the base excision repair (BER) pathway which is involved in the repair of damaged nucleobases by reactive oxygen species, UVA irradiation, and DNA alkylating agents. Therefore, it is expected that the inhibition or modulation of the AP site ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2019.115160

    authors: Abe YS,Sasaki S

    更新日期:2019-12-15 00:00:00

  • A synthesis of (R)-recifeiolide by the aid of biochemical reaction as the key-step.

    abstract::(R)-Recifeiolide, a naturally occurring macrolactone, was synthesized in optically pure form by the aid of biocatalysts. Lipase-catalyzed lactonization of the racemic precursor afforded the desired compound with a concomitant kinetic resolution. The optically active acyclic precursor could be synthesized by the reduct...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(00)82105-7

    authors: Mochizuki N,Yamada H,Sugai T,Ohta H

    更新日期:1993-07-01 00:00:00

  • 2- and 3-substituted imidazo[1,2-a]pyrazines as inhibitors of bacterial type IV secretion.

    abstract::A novel series of 8-amino imidazo[1,2-a]pyrazine derivatives has been developed as inhibitors of the VirB11 ATPase HP0525, a key component of the bacterial type IV secretion system. A flexible synthetic route to both 2- and 3-aryl substituted regioisomers has been developed. The resulting series of imidazo[1,2-a]pyraz...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2014.09.036

    authors: Sayer JR,Walldén K,Pesnot T,Campbell F,Gane PJ,Simone M,Koss H,Buelens F,Boyle TP,Selwood DL,Waksman G,Tabor AB

    更新日期:2014-11-15 00:00:00

  • Synthesis, nicotinic acetylcholine receptor binding, in vitro and in vivo pharmacology properties of 3'-(substituted pyridinyl)-deschloroepibatidine analogs.

    abstract::Over the last several years we have synthesized and studied the in vitro and in vivo nAChR pharmacological properties of epibatidine (4) analogs. In this study we report the synthesis, nAChR in vitro and in vivo pharmacological properties of 3'-(substituted pyridinyl)-deschloroepibatidine analogs (5a-e and 6a-e). All ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.07.021

    authors: Ondachi PW,Ye Z,Castro AH,Luetje CW,Damaj MI,Mascarella SW,Navarro HA,Carroll FI

    更新日期:2015-09-01 00:00:00

  • Synthesis, structural characterization and cell death-inducing effect of novel palladium(II) and platinum(II) saccharinate complexes with 2-(hydroxymethyl)pyridine and 2-(2-hydroxyethyl)pyridine on cancer cells in vitro.

    abstract::Four palladium(II) and platinum(II) saccharinate (sac) complexes with 2-(hydroxymethyl)pyridine (2-hmpy) and 2-(2-hydroxyethyl)pyridine (2-hepy), namely trans-[Pd(2-hmpy)2(sac)2]·H2O (1), trans-[Pt(2-hmpy)2(sac)2]·3H2O (2), trans-[Pd(2-hepy)2(sac)2] (3) and trans-[Pt(2-hepy)2(sac)2] (4), have been synthesized and char...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2013.08.050

    authors: Ari F,Aztopal N,Icsel C,Yilmaz VT,Guney E,Buyukgungor O,Ulukaya E

    更新日期:2013-11-01 00:00:00

  • Synthesis of 11C-labelled (R)-OHDMI and CFMME and their evaluation as candidate radioligands for imaging central norepinephrine transporters with PET.

    abstract::(R)-1-(10,11-Dihydro-dibenzo[b,f]azepin-5-yl)-3-methylamino-propan-2-ol ((R)-OHDMI) and (S,S)-1-cyclopentyl-2-(5-fluoro-2-methoxy-phenyl)-1-morpholin-2-yl-ethanol (CFMME) were synthesized and found to be potent inhibitors of norepinephrine reuptake. Each was labelled efficiently in its methyl group with carbon-11 (t(1...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2006.10.065

    authors: Schou M,Pike VW,Sóvágó J,Gulyás B,Gallagher PT,Dobson DR,Walter MW,Rudyk H,Farde L,Halldin C

    更新日期:2007-01-15 00:00:00

  • On the nature of the irreversible inhibition of histidine ammonia lyase by cysteine and dioxygen.

    abstract::The irreversible inhibition of histidine ammonia lyase by L-cysteine and dioxygen has been reexamined. After denaturation and consecutive digestion of the inhibited enzyme by trypsin and endoproteinase Glu-C, the generated chromophoric system (lambda max = 340 nm) remained intact and was isolated in an octapeptide con...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/0968-0896(96)00091-0

    authors: Weber K,Rétey J

    更新日期:1996-07-01 00:00:00

  • Comparative reactivity analysis of small-molecule thiol surrogates.

    abstract::Targeted covalent inhibitors represent an increasingly popular approach to modulate challenging drug targets. Since covalent and non-covalent interactions are both contributing to the affinity of these compounds, evaluation of their reactivity is a key-step to find feasible warheads. There are well-established HPLC- a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2020.115357

    authors: Petri L,Ábrányi-Balogh P,Varga PR,Imre T,Keserű GM

    更新日期:2020-04-01 00:00:00

  • STD-NMR studies of two acceptor substrates of GlfT2, a galactofuranosyltransferase from Mycobacterium tuberculosis: epitope mapping studies.

    abstract::The major structural component of the mycobacterial cell wall, the mycolyl-arabinogalactan-peptidoglycan complex, possesses a galactan core composed of approximately 30 galactofuranosyl (Galf) resides attached via alternating beta-(1-->6) and beta-(1-->5) linkages. Recent studies have shown that the entire galactan is...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2010.05.069

    authors: Szczepina MG,Zheng RB,Completo GC,Lowary TL,Pinto BM

    更新日期:2010-07-15 00:00:00

  • Synthesis of pdCpAs and transfer RNAs activated with thiothreonine and derivatives.

    abstract::N,S-diprotected L-thiothreonine and L-allo-thiothreonine derivatives were synthesized using a novel chemical strategy, and used for esterification of the dinucleotide pdCpA. The aminoacylated dinucleotides were then employed for the preparation of activated suppressor tRNA(CUA) transcripts. Thiothreonine and allo-thio...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.02.024

    authors: Chen S,Fahmi NE,Nangreave RC,Mehellou Y,Hecht SM

    更新日期:2012-04-15 00:00:00

  • Beta-hairpin and beta-sheet formation in designed linear peptides.

    abstract::Recent knowledge about the determinants of beta-sheet formation and stability has notably been improved by the structural analysis of model peptides with beta-hairpin structure in aqueous solution. Several experimental studies have shown that the turn region residues can not only determine the stability, but also the ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(98)00215-6

    authors: Ramírez-Alvarado M,Kortemme T,Blanco FJ,Serrano L

    更新日期:1999-01-01 00:00:00

  • Design, synthesis, and biological evaluation of amide imidazole derivatives as novel metabolic enzyme CYP26A1 inhibitors.

    abstract::All-trans-retinoic acid (ATRA) as a physiological metabolite of vitamin A is widely applied in the treatment of cancer, skin, neurodegenerative and autoimmune diseases. CYP26A1 enzyme, induced by ATRA in liver and target tissues, metabolizes ATRA into 4-hydroxyl-RA. Inhibition of CYP26A1 metabolic enzyme represents a ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2015.08.019

    authors: Sun B,Liu K,Han J,Zhao LY,Su X,Lin B,Zhao DM,Cheng MS

    更新日期:2015-10-15 00:00:00

  • Radiolabeling of RGD peptide and preliminary biological evaluation in mice bearing U87MG tumors.

    abstract::2-[(18)F]Fluoroethyl azide ([(18)F]FEA) and terminal alkynyl modified propioloyl RGDfK were selected in this study. [(18)F]FEA was prepared by nucleophilic radiofluorination of 2-azidoethyl 4-toluenesulfonate with radiochemical yield of 71 ± 4% (n = 5, decay-corrected). We assessed the various conditions of the CuAAC ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2012.04.037

    authors: Li J,Shi L,Jia L,Jiang D,Zhou W,Hu W,Qi Y,Zhang L

    更新日期:2012-06-15 00:00:00

  • Conjugation of cell-penetrating peptides leads to identification of anti-HIV peptides from matrix proteins.

    abstract::Compounds which inhibit the HIV-1 replication cycle have been found amongst fragment peptides derived from an HIV-1 matrix (MA) protein. Overlapping peptide libraries covering the whole sequence of MA were designed and constructed with the addition of an octa-arginyl group to increase their cell membrane permeability....

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2011.12.055

    authors: Narumi T,Komoriya M,Hashimoto C,Wu H,Nomura W,Suzuki S,Tanaka T,Chiba J,Yamamoto N,Murakami T,Tamamura H

    更新日期:2012-02-15 00:00:00

  • Synthesis and anticancer activity of benzyloxybenzaldehyde derivatives against HL-60 cells.

    abstract::A series of benzyloxybenzaldehyde derivatives were prepared and tested against the HL-60 cell line for anticancer activity. Preliminary structure-activity relationships were established. It was discovered that 2-(benzyloxy)benzaldehyde (17), 2-(benzyloxy)-4-methoxybenzaldehyde (26), 2-(benzyloxy)-5-methoxybenzaldehyde...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bmc.2004.12.026

    authors: Lin CF,Yang JS,Chang CY,Kuo SC,Lee MR,Huang LJ

    更新日期:2005-03-01 00:00:00

  • Synthesis, cellular internalization and photodynamic activity of glucoconjugated derivatives of tri and tetra(meta-hydroxyphenyl)chlorins.

    abstract::Glucoconjugated tri and tetra(meta-hydroxyphenyl)chlorins have been synthesized in order to explore how glucoconjugation of the macrocycle affects the photoactivity of the molecule. Internalization processes, photosensitizing efficacy of TPC(m-O-GluOH)(3) and TPC(m-O-GluOH)(4), in HT29 human adenocarcinoma cells have ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(03)00050-6

    authors: Laville I,Figueiredo T,Loock B,Pigaglio S,Maillard P,Grierson DS,Carrez D,Croisy A,Blais J

    更新日期:2003-04-17 00:00:00

  • New highly active taxoids from 9beta-dihydrobaccatin-9,10-acetals. Part 4.

    abstract::It was shown that a new taxane analogue 3, which exhibited both in vitro antitumor activity and in vivo efficacy by both i.v. and p.o. administration, was prone to be metabolized by human liver microsomes. We identified a major metabolite, M-1, generated by human liver microsomes as 20a, a hydroxylated compound at the...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章

    doi:10.1016/s0968-0896(03)00454-1

    authors: Takeda Y,Uoto K,Chiba J,Horiuchi T,Iwahana M,Atsumi R,Ono C,Terasawa H,Soga T

    更新日期:2003-10-01 00:00:00