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

Abstract

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.

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

“…Thus, these compounds can serve as promising lead candidates for further investigations. 1,2,3- Triazole-containing indole derivatives 14 (IC 50 : 9.07-47.11 μm, MTT assay) and 15 (IC 50 : 15.25-38.68 μm, MTT assay) show considerable activity against A549 cells, and the most potent compound 14a (IC 50 : 9.07 μm) is not inferior to doxorubicin (IC 50 : 4.39 μm) (Srinivas et al, 2020;Suryapeta et al, 2020).…”

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

“…[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. It is also present in proteins in the form of amino acid i. e. tryptophan.…”

“…Compounds having amino acid moieties are also known to possess favorable biological and pharmacological properties [30–35] . Notably, the small peptides are being considered as potential alternatives to the presently available antibiotics and/or possible entities in other medical field [14–15,36−38] . Considering all these observations and due to our ongoing efforts in the synthesis of library of new chemical entities (NCEs) we designed a template A (Figure 1) that contains a dipeptide along with the structural features of naproxen and tryptophan and a 1,4‐disubstituted 1,2,3‐triazole ring.…”

“…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] . The indole nucleus, an important heterocyclic moiety is prevalent in many natural and unnatural bioactive molecules.…”

Synthesis, Biological Evaluation and Docking Study of Etodolac-Triazole Conjugate

“…Triazoles which are an important class of heterocyclic compounds, have been studied for over a century and continue to attract considerable attention because of many biological activities [9][10][11][12][13][14][15][16][17][18][19][20][21]. We anticipated that integration of structural features of etodolac Fig.…”