Synthesis and Antibacterial Evaluation of Carboxamide Derivatives of Amino Acids

Pande, Samay; Utale, Prashant S Utale Prashant S; Gholse, S. B.; Tekade, P. V.; Patil, Sudhakar G.

doi:10.1007/s11094-014-1040-8

Cited by 10 publications

(9 citation statements)

References 12 publications

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“…The aromatic ring was manipulated by introducing electron withdrawing and donating groups and hydrogen bond donors and acceptors. Carboxylic acid 1 was coupled under Steglich-like conditions (Pande et al, 2014) with alcohols 2a-m furnishing the intended esters 3a-m . Ester 3k' was obtained through deprotection of 3k under acidic conditions, and compounds 3l' and 3m' were generated from the reduction of 3l and 3m , respectively.…”

Section: Resultsmentioning

confidence: 99%

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Structure-Based and Molecular Modeling Studies for the Discovery of Cyclic Imides as Reversible Cruzain Inhibitors With Potent Anti-Trypanosoma cruzi Activity

et al. 2019

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Chagas disease causes ~10,000 deaths each year, mainly in Latin America, where it is endemic. The currently available chemotherapeutic agents are ineffective in the chronic stage of the disease, and the lack of pharmaceutical innovation for Chagas disease highlights the urgent need for the development of new drugs. The enzyme cruzain, the main cysteine protease of Trypanosoma cruzi, has been explored as a validated molecular target for drug discovery. Herein, the design, molecular modeling studies, synthesis, and biological evaluation of cyclic imides as cruzain inhibitors are described. Starting with a micromolar-range cruzain inhibitor (3a, IC50 = 2.2 μM), this molecular optimization strategy resulted in the nanomolar-range inhibitor 10j (IC50 = 0.6 μM), which is highly active against T. cruzi intracellular amastigotes (IC50 = 1.0 μM). Moreover, most compounds were selective toward T. cruzi over human fibroblasts, which were used as host cells, and are less toxic to hepatic cells than the marketed drug benznidazole. This study enabled the discovery of novel chemical diversity and established robust structure-activity relationships to guide the design of optimized cruzain inhibitors as new trypanocidal agents.

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Section: Resultsmentioning

confidence: 99%

“…The synthesis of compounds 9d-f and 9h-j was carried out by refluxing in toluene with triethylamine as the catalyst. The stereocenter of the carboxylic acids was observed to have the absolute configuration of R (Pande et al, 2014). The amino acid side chains gave rise to hydrophobic fragments.…”

Section: Resultsmentioning

confidence: 99%

Structure-Based and Molecular Modeling Studies for the Discovery of Cyclic Imides as Reversible Cruzain Inhibitors With Potent Anti-Trypanosoma cruzi Activity

et al. 2019

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“…For example, using baicalein as the parent compound to synthesize novel neuroprotective agents by combination with amino acids, carboxamide derivatives are synthesized by the reaction of amino acids and phthalic anhydride, which shows better antibacterial activity, compared with baicalein shows derivatives of 3-aminomethylglaucine have shown higher radical scavenging activity than that of 3-aminomethylglaucine and glaucine. [23][24][25] There are 24 small-molecule drugs have been approved by FDA in 2019, among all these drugs, 13 contain a residue of amino acids, di-amines or amino-alcohols, which are commonly considered to be derived from the parent amino acids. 26 Therefore, modification of the structure of pinocembrin by introducing a fragment containing an amino acid residue probably lead to a generation of compounds with useful biological properties.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel Pinocembrin Amino Acid Derivatives and Their Antiaging Effect on Caenorhabditis elegans via the Modulating DAF-16/FOXO

Wang¹,

Feng²,

Du³

et al. 2021

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Pinocembrin is a dihydroflavonoid, which is widely found in several plant species. Although pinocembrin has good pharmacological activity, it has poor water solubility and low bioavailability. Therefore, we have modified the structure of pinocembrin with a combination of different amino acids to solve this problem. Moreover, the effect of the antiaging activity of them has not been explored. We aim to investigate the effect of pinocembrin and its amino acid derivatives on the aging of Caenorhabditis elegans. Methods: Pinocembrin was spliced with different amino acids in order to obtain their corresponding derivatives. The preliminary research of pinocembrin and its amino acid derivatives on antiaging effect was studied by using the C. elegans model. Among all the compounds, the one shows the best antiaging effect was then studied on antiaging mechanism. The protective effect on nematodes under emergency conditions was explained by detecting the ROS content and sod-3p::GFP fusion protein expression in nematodes; the possible anti-aging mechanism of nematodes was determined by DAF-16 nuclear localization experiment and the survival curve of transgenic nematodes model under stress conditions. Results: Pb-3 showed the best effect on increasing tolerance to thermal and oxidative stress and reduce the accumulation of lipofuscin. In the assay of C. elegans, pb-3 reduced intracellular ROS accumulation. Application of pb-3 to the transgenic mutant TJ356 induced the translocation of the transcription factor DAF-16 from the cytosol to the nucleus, and modulated the expression of SOD-3 (downstream genes of daf-16), which regulates longevity in C. elegans. Moreover, pb-3 did not prolong the lifespan of daf-16, age-1, daf-2 and hsp16.2 mutants, suggesting that these genetic pathways are involved in mediating the antiaging effects of pb-3. Conclusion:The antioxidant and antiaging properties of pb-3 may involve in the DAF-16/ FOXO transcription process. Pinocembrin amino acid derivatives might be a novel agent for antiaging therapy.

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“…64, No. 6 (2021) increase in reaction time [12,15,17,29]. Conducting the practice in an acetic acid environment makes the method relatively efficient and economical [30,31].…”

Section: Resultsmentioning

confidence: 99%

“…It should be noted that the amides N,Nphthaloylglycine may be a class of antiepileptic drugs in the future [16]. Carboxamides derived from N-phthaloyl-α-amino acids have also been found to be active against bacteria, especially the activity of carboxamides that retain the cyclopropyl ring has been highly evaluated [17]. In addition, the high anti-inflammatory potential of carboxamides has been proven experimentally [18].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of new Amides based on N-Phthaloyl-α-Amino Acids

2021

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N-phthaloyl derivatives of aliphatic α-amino acids were synthesized using phthalanhydride under standard conditions. The optimization reaction carried out by the thermal method to obtain the amides of these N-phthaloyl amino acids resulted in transimitted rather than amidation. The target amides of N-phthaloyl-α-amino acids were obtained by acylation of the amine with the corresponding acid chloroanhydrides in dichloromethane. These results were compared with the results of a similar acylation in a non-polar solvent (benzene). The dependence of the direction of the reaction on the duration of the acylation and the amount of amine used was established. The conditions for the formation of the corresponding N-phthaloyl-α-amino acid amides and asymmetric phthalic acid diamides were found. It is noteworthy that the formation of diamides is directly proportional to the equivalent amount of amine and the duration of the reaction, which makes it possible to purposefully control the synthesis in one reactor.

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Synthesis and Antibacterial Evaluation of Carboxamide Derivatives of Amino Acids

Cited by 10 publications

References 12 publications

Structure-Based and Molecular Modeling Studies for the Discovery of Cyclic Imides as Reversible Cruzain Inhibitors With Potent Anti-Trypanosoma cruzi Activity

Structure-Based and Molecular Modeling Studies for the Discovery of Cyclic Imides as Reversible Cruzain Inhibitors With Potent Anti-Trypanosoma cruzi Activity

Synthesis of Novel Pinocembrin Amino Acid Derivatives and Their Antiaging Effect on Caenorhabditis elegans via the Modulating DAF-16/FOXO

Synthesis of new Amides based on N-Phthaloyl-α-Amino Acids

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