Synthesis, Docking, Computational Studies, and Antimicrobial Evaluations of New Dipeptide Derivatives Based on Nicotinoylglycylglycine Hydrazide

Abstract

Within a series of dipeptide derivatives (5–11), compound 4 was refluxed with d-glucose, d-xylose, acetylacetone, diethylmalonate, carbon disulfide, ethyl cyanoacetate, and ethyl acetoacetate which yielded 5–11, respectively. The candidates 5–11 were characterized and their biological activities were evaluated where they showed different anti-microbial inhibitory activities based on the type of pathogenic microorganisms. Moreover, to understand modes of binding, molecular docking was used of Nicotinoylglycine derivatives with the active site of the penicillin-binding protein 3 (PBP3) and sterol 14-alpha demethylase’s (CYP51), and the results, which were achieved via covalent and non-covalent docking, were harmonized with the biological activity results. Therefore, it was extrapolated that compounds 4, 7, 8, 9, and 10 had good potential to inhibit sterol 14-alpha demethylase and penicillin-binding protein 3; consequently, these compounds are possibly suitable for the development of a novel antibacterial and antifungal therapeutic drug. In addition, in silico properties of absorption, distribution, metabolism, and excretion (ADME) indicated drug likeness with low to very low oral absorption in most compounds, and undefined blood–brain barrier permeability in all compounds. Furthermore, toxicity (TOPKAT) prediction showed probability values for all carcinogenicity models were medium to pretty low for all compounds.

Nα-1, 3-Benzenedicarbonyl-Bis-(Amino Acid) and Dipeptide Candidates: Synthesis, Cytotoxic, Antimicrobial and Molecular Docking Investigation

“…Our research group has published several studies indicating that peptide candidates are promising as potential anticancer drugs, [5][6][7][8][9][10][11][12][13][14][15] anti-inflammatory and analgesic drugs, 16 and as antibacterial drugs. [17][18][19][20][21][22][23][24][25][26][27][28] The incidence of microbial infections in cancer patients increases due to the low circulating neutrophil levels in these patients in addition to the disruption of the microbial flora. Thus, the objective of the current study is to synthesize a new peptide derivative with multiple biological activities including anticancer, anti-inflammatory, and antibacterial activities to be considered as potential candidates used in the treatment of cancer.…”

Design, Synthesis and Molecular Docking of New Benzimidazole Derivatives of Potential Antimicrobial Activity as DNA Gyrase and Topoisomerase IV Inhibitors

“…The bacterial activity of the active compounds (having inhibition zones (IZ) ≥ 16 mm) was then evaluated using the two-fold serial dilution technique [49,50]. Two-fold serial dilutions of the tested compounds solutions were prepared using the proper nutrient broth.…”

“…The antimicrobial activity has been primarily evaluated as the observed growth inhibition zones (mm) resulting from 100 µl of stock solution (10 mg/ml) of the tested compounds and reference drug standards. (Table 1) Minimum inhibitory concentrations (MIC µg/mL) were then determined for compounds exhibiting significant growth inhibition zones ≥ 16mm using two-fold serial dilution method [49,50] (Table 2). Also, (Figs.…”

Synthesis, Characterization, In Vitro Anticancer Potentiality, and Antimicrobial Activities of Novel Peptide–Glycyrrhetinic-Acid-Based Derivatives

“…However, due to the high hydrophobicity and poor blood serum solubilization of the pentacyclic triterpenoids, GA use as a cytotoxic medicine in the treatment of cancer disease is limited. Up until now, numerous studies were directed to structural modifications to enhance GA bioavailability, selectively, and cytotoxicity [ 26 , 27 , 28 , 29 , 30 ]. Amino acids are the primary substance, which support biological life activities, producing very important roles.…”

“…Based on the afro-mentioned investigations, aiming to modify and improve the bioactivity of GA and in continuation of our strenuous efforts in the field of discovery of new potent anticancer and antimicrobial agents [ 26 , 27 , 28 , 29 , 30 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ], this work represents a facile structural modification strategy to synthesize novel 18β-glycyrrhetinic amide derivatives via its coupling with different amino acids. The new compounds were evaluated as anticancer candidates against three human cancer cells; colon cancer HCT-116, breast cancer (MCF-7), and liver cancer (HepG-2) cell lines.…”