Acyclic Pyrazolo[3,4- d ]Pyrimidine Nucleoside as Potential Leishmaniostatic Agent *

Hasan, A.; Satyanarayana, M.; Mishra, Ashish Kumar; Bhakuni, D. S.; Pratap, Ramendra; Dube, Anuradha; Guru, P. Y.

doi:10.1081/15257770500379017

Cited by 9 publications

(4 citation statements)

References 9 publications

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“…At a higher concentration of 400 μM, compounds 11-17 inhibited the promastigotes pro-Scheme 1. Synthesis of biaryl piperidine derivatives (11)(12)(13)(14)(15)(16)(17)(18)(19) 5). The IC 50 was calculated from the dose response curve using the linear interpolation equation and was found to be 17 μM.…”

Section: Antileishmanial Activitymentioning

confidence: 99%

“…The seriousness of the disease prompted several research groups to work on the development of new antileishmanial agents and the class of scaffolds explored includes various quinolines, [10 -13] chalcones, [14,15] nitroimidazole, [16] triazolopyrimidine, [17] pyrazolopyrimidine, [18,19] aminopyrazole, [20] triazine, [21,22] quinazoline, [23] thymidine, [24] triterpenoids, [25] and quinazolinone. [26] The isolation and synthesis of a new class of biaryl naphthylisoquinoline alkaloid ancistroealaine A (1a) from Ancistrocladus ealaensis and other alkaloids (1b, 1c), and their antileishmanial activity has generated interest in the development of new antileishmanial agents.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis of Biaryl Piperidine Derivatives and Their Evaluation as Potential Antileishmanial Agents against Leishmania donovani Strain Ag83

Rathnakar

Sinha

Prasad

et al. 2021

Chemistry & Biodiversity

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We have developed a new series of simple biaryl piperidine derivatives (11-19) based on biaryl naphthylisoquinoline alkaloid Ealamine-A. The target compounds were synthesized, analyzed by spectral data, and evaluated for antileishmanial activity against Leishmania donovani strain Ag83 by MTT assay. The compounds have shown the best to moderate antileishmanial activity. The 5'-fluoro-2'-methoxyphenyl derivative 14 and 3',5'-difluorophenyl derivative 16 have inhibited the promastigotes by 86 % and 85 % after 24 h and 92 % and 91 % after 48 h incubation, respectively, at 400 μM concentration. The % inhibition was lower with the lowering of the concentration and increased with the incubation time. Compounds 12, 15, and 18 have solubility issues and proved to be less active than the rest of the compounds. Molecular docking studies were performed on selective active compounds and the results indicate that these compounds may act by binding to the Leishmanolysin and the docking scores are in good correlation with the antileishmanial activity. These results provide an initial insight into the design of new therapeutics for neglected tropical diseases.

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Section: Antileishmanial Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Design, Synthesis of Biaryl Piperidine Derivatives and Their Evaluation as Potential Antileishmanial Agents against Leishmania donovani Strain Ag83

Rathnakar

Sinha

Prasad

et al. 2021

Chemistry & Biodiversity

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“…Indeed, the absence of the N7 residue in H4app, which is believed to be the most relevant metal binding site in natural purines (exposed at the major groove of DNA), has raised high and broad interest regarding its potential applications. In this context, several pharmacological properties have been already described for pyrazolo[3,4-d]pyrimidine ligands such as antibacterial and antifungal, antiparasite, or antiproliferative agents . Likewise, they have been reported as adenosine antagonists and enzyme inhibitors .…”

Section: Introductionmentioning

confidence: 98%

Structural Consequences of the N7 and C8 Translocation on the Metal Binding Behavior of Adenine

et al. 2013

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7-Deaza-8-aza-adenine, namely 4-aminopyrazolo[3,4-d]pyrimidine (H4app), is a bioisoster of adenine (Hade) resulting from the translocation of N7 and C8 atoms on the purine moiety. With the aim of studying the influence of this translocation on the metal binding abilities of H4app, we have prepared and structurally characterized two ternary copper(II) complexes having H4app and one N-benzyl-iminodiacetate chelator (MEBIDA or FBIDA, with a methyl or fluoro group in para- of the benzyl aromatic ring): [Cu(2)(MEBIDA)(2)(μ(2)-N1,N8-H4app)(H(2)O)(2)]·4H(2)O (1) and [Cu(4)(FBIDA)(4)(μ(2)-N8,N9-H4app)(2)(H(2)O)]·3.5H(2)O (2). Furthermore, thermal, spectral, and magnetic properties have been also investigated. In 1, H(N9)4app is disordered over two equally pondered positions and the μ(2)-N1,N8 coordination mode is assisted by N6-H···O and N9-H···O intramolecular interactions, respectively. The acyclic nonlinear molecular topology of 2 is strongly influenced by two intramolecular H-bonding interactions (O-H···O-carboxylate) involving the apical aqua ligand of a terminal Cu(II) atom. Thus, both compounds have in common the Cu-N8 bond. In order to better understand our limited structural information, DFT calculations for the individual tautomers of H4app as well as mononuclear Cu(II) model systems have been carried out. According to previous results, we conclude that H(N9)4app is the most stable tautomer followed by H(N8)4app. When N9 and N8 are metalated, then the tautomer H(N1)4app can come into play as observed in compound 2. Likewise, the findings concerning compound 1 suggest that the formation of a Cu-N1 bond in H4app results was favored compared to neutral adenine, for which only one case has been reported with such coordination despite the large variety of related Cu(II)-Hade described in the literature.

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“…Similarly, oxazole and pyrimidine‐containing heterocycles have shown various types of biological activities [13,14] . The molecular hybrids of oxazolyl‐pyrimidines have been reported as promising agents for treating hyperproliferative disorders and as antitubercular and antibacterial agents [15] .…”

Section: Introductionmentioning

confidence: 99%

Development of New 5‐(Oxazol‐2‐yl)Pyrimidine Derivatives with Promising Anticancer Activities

Shyam Kumar,

Ramesh,

Sridhar

et al. 2023

ChemistrySelect

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A novel series of oxazolyl‐pyrimidine derivatives (11 a–j) have been synthesized and structures were confirmed by spectral data. The synthesized compounds were assessed for cytotoxic profile towards human cervix cancer (SiHa), lung cancer (A549), breast cancer (MCF‐7), and colon cancer (Colo‐205) cell lines by employing MTT assay and using etoposide as the positive control. The heteroaryl compounds having the terminal pyridyl (11 a) and thiazolyl (11 b) groups showed superior cytotoxic potency against cervix and lung cancer cell lines and varying methoxy substituted derivatives 11 c–11 e have excellent to good cytotoxic properties. Compound 11 a and 11 b have IC50 values in the range of 0.01±0.0034 to 0.17±0.059 μM and 0.10±0.038 to 0.66±0.077 μM respectively in the tested cell lines. The selected compounds 11 a and 11 b were studied by molecular docking to assess the binding interactions, binding energies, and possible mechanisms. The in‐silico ADME properties were calculated and all the compounds have the desired properties of drug‐like molecules. The toxicity results indicate that all the compounds are free from toxicity except 11 j, which has high tumorigenic properties. The optimized structure, energies of frontier molecular orbitals, molecular electrostatic potential, and NLO parameters for compound 11 a were determined using DFT/B3LYP level with a 6‐311++G(d,p) basis set.

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Acyclic Pyrazolo[3,4- d ]Pyrimidine Nucleoside as Potential Leishmaniostatic Agent *

Cited by 9 publications

References 9 publications

Design, Synthesis of Biaryl Piperidine Derivatives and Their Evaluation as Potential Antileishmanial Agents against Leishmania donovani Strain Ag83

Design, Synthesis of Biaryl Piperidine Derivatives and Their Evaluation as Potential Antileishmanial Agents against Leishmania donovani Strain Ag83

Structural Consequences of the N7 and C8 Translocation on the Metal Binding Behavior of Adenine

Development of New 5‐(Oxazol‐2‐yl)Pyrimidine Derivatives with Promising Anticancer Activities

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