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.
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.
Background:
Benzothiazine derivatives, because of their various biological activities have
attracted particular attention in Med Chem and drug discovery efforts. The synthetic modifications of
1,2-benzothiazine 1,1-dioxides have been undertaken in order to explore and identify novel compounds
or new analogues possessing promising biological activities. In our effort we have designed -oxicam
derived bezothiazine-1,2,3-triazole derivatives as potential antibacterial agents.
Methods:
These compounds were synthesized via a multi-step sequence involving the Cu catalyzed azide-
alkyne cycloaddition (CuAAC) as a key step. The CuAAC proceeded at room temperature in DMF
to afford 26 novel molecules in good (70-90%) yields.
Results:
All these compounds were tested for their antibacterial properties against four strains of bacterial
microorganisms and subsequently cytotoxic properties against lung and colon cancer cell lines.
The compound 4e showed activities against majority of the bacterial species used (nearly comparable
to amoxicillin, ciprofloxacin and ofloxacin against P. vulgaris) whereas 4d and 4f showed cytotoxicities
selective towards cancer cells.
Conclusion:
The present bezothiazine-1,2,3-triazole framework represents a new template for the
identification of novel and potent antibacterial/anticancer agents.
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).
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