2-(6-Methoxynaphthalen-2-yl)propionic acid (1,3-dimethyl­butylidene)hydrazide

Neeraja²,

Naveen

et al. 2020

ChemistrySelect

A series of peptide based new tryptophan-1,2,3-triazolenaproxen derivatives were explored as prospective antibacterial / cytotoxic agents. These derivatives were prepared via a multistep method involving CuAAC as a key step and characterized by spectral data. The synthesized derivatives were evaluated for their antimicrobial activities against one Gram-positive (S. aureus) and three Gram-negative (E. coli, K. pneumoniae and P. vulgaris) bacteria using an agar-well diffusion protocol where amoxycillin was used as a reference compound. Most of these compounds showed antibacterial activities when tested at 0.4 mg / 50 μl concentration. Compound 9 e i. e. N-( 1methoxynaphthalen-2-yl)propanamido)propanamide exhibited good activities against all the strains. The potential DNA gyrase inhibitory activity of this compound was investigated by molecular docking studies carried out using Autodock Vina software. Compound 9 e showed an impressive ΔG bind of À 10.0 kcal/mol. The cytotoxicity of the obtained compounds was also assessed against A549 cancer cell line (human lung carcinoma) by an MTT assay. Several of these compounds showed promising activity while 9 e showed lowest IC 50 value. A brief SAR for both antibacterial / cytotoxic activities of compounds tested is presented. Overall, compound 9 e has emerged as an initial hit molecule for further study.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis, Chemotherapeutic Screening and Docking Studies of NSAID Inserted Peptide‐Triazole Hybrid Molecules

Neeraja²,

Naveen

et al. 2020

ChemistrySelect

“…The derivatives of naproxen (a well-known NSAID) are known to possess a broad array of biological properties including antimicrobial, antifungal, antibacterial, antimalarial, antiviral and antitumor activities. [5][6][7][8][9][10][11][12] On the other hand compounds containing the 1,2,3-triazole framework (a bioisostere of peptide) displayed various pharmacological activities. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] The indole nucleus, an important heterocyclic moiety is prevalent in many natural and unnatural bioactive molecules.…”

Section: Introductionmentioning

confidence: 99%

“…The derivatives of naproxen (a well‐known NSAID) are known to possess a broad array of biological properties including antimicrobial, antifungal, antibacterial, antimalarial, antiviral and antitumor activities [5–12] . On the other hand compounds containing the 1,2,3‐triazole framework (a bioisostere of peptide) displayed various pharmacological activities [13–29] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Biological Evaluation and In silico Studies of Compounds Based on Tryptophan‐Naproxen‐Triazole Hybrids

Neeraja²,

Banothu

et al. 2020

ChemistrySelect

Self Cite

A hybrid of three different frameworks e. g. tryptophan, naproxen and triazole has been explored for the identification of potential antibacterial / anticancer agents. A library of new compounds, designed based on this hybrid framework was synthesized via a multi‐step sequence using the Cu(I)‐catalyzed azide‐alkyne cycloaddition (CuAAC) as the key reaction step. Thus the terminal alkyne obtained via the reaction of tryptophan ester with naproxen followed by N‐propargylation of the indole ring was coupled with a range of organic azides to give the desired products (through the formation of triazole ring) in good to acceptable yields. The in vitro antibacterial screening of these compounds against S. aureus (Gram‐positive) as well as E. coli and K. pneumoniae (Gram‐negative) strains identified several hits with moderate to good activities with 4‐(4‐((3‐(3‐methoxy‐2‐(2‐(6‐methoxynaphthalen‐2‐yl)propanamido)‐3‐oxopropyl)‐1H‐indol‐1‐yl)methyl)‐1H‐1,2,3‐triazol‐1‐yl)benzoic acid (6 n) being the best (MIC∼25 μg/mL across all the strains). Several compounds e. g. analogues containing a (4‐chlorophenyl)amino)‐2‐oxoethyl moiety (6 e) and (4‐nitrophenyl)amino)‐2‐oxoethyl moiety (6 h) attached to the triazole ring also showed cytotoxic activities when tested against A549 cancer cell line (IC50=39.35 and 28.52 μg/mL, respectively).

Synthesis, biological evaluation, and docking study of a series of 1,4‐disubstituted 1,2,3‐triazole derivatives with an indole‐triazole‐peptide conjugate

Journal of Heterocyclic Chem

Neeraja²,

Banothu

et al. 2020

A series of new compounds containing an indole‐triazole‐peptide conjugate were designed as potential agents possessing the dual anti‐bacterial and anticancer activities. Accordingly, 20 compounds were prepared via a multi‐step synthesis involving the copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) as a key step in moderate to high yield. All the synthesized compounds were purified by chromatographic techniques and characterized by IR, 1H and 13C NMR and mass spectral data. The synthesized derivatives were screened for their antimicrobial activities against one gram‐positive (Staphylococcus aureus) and three gram‐negative (Escherichia coli, Klebsiella pneumonia, and Proteus vulgaris) bacteria using an agar‐well diffusion method. Most of the compounds showed moderate to reasonable antibacterial activities especially the compound 9e that showed good activities against all the strains. The potential of DNA gyrase inhibitory activity of this compound was assessed by using molecular docking studies in silico carried out using Autodock Vina software. The low ΔGbind value (−9.4 Kcal/mol) of compound 9e suggested its good interactions with the target protein in silico. The cytotoxic activities of some of the compounds synthesized were evaluated via a MTT assay using the human lung cancer cell line A549. Several compounds showed promising activities among which compound 9b, 9k, and 9e showed low IC50 values.