Synthesis, Pharmacological and Toxicological Screening of Penicillin–Triazole Conjugates (PNTCs)

Abstract

A series of hybrid antimicrobial compounds were prepared by carboxylic acid protection of 6-aminopenicillanic acid using benzyl alcohol and thionyl chloride succeeded by azide displacement using trifluoromethanesulfonyl azide in dichloromethane. The azide thus formed was reacted with substituted alkynes to furnish benzyl-protected penicillin–triazole conjugates. Benzyl deprotection of the conjugates resulted in furnishing PNTCs under water methanol mixture using Pd/C as a catalyst. The PNTCs (7a–j) formed were screened for in vitro antibacterial potency against pathogenic strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes and antifungal potency against Candida albicans, Aspergillus niger, and Aspergillus clavatus. Further antimicrobial evaluation revealed compounds 7c, 7d, 7e, 7g, and 7i to be the most compounds of the series with minimum inhibitory concentration value for antibacterial in the range 0.5–50 μg/mL and for antifungal in the range 9–300 μg/mL. Toxicological analysis documented for compounds 7c, 7d, 7e, 7g, and 7i revealed compound 7i to be the most promising member of the series with 1000 and 500 mg/kg LD50, and no-observed-adverse-effect level to facilitate future clinical studies of the same.

Bioisosteric Replacement of Amide Group with 1,2,3-Triazoles in Acetaminophen Addresses Reactive Oxygen Species-Mediated Hepatotoxic Insult in Wistar Albino Rats

“…The term “bioisosterism” is used to define a phenomenon in which molecules with similar physical and chemical properties exhibit broadly similar biological properties . In the contemporary practice of drug design, the concept of bioisosteric replacement has been adopted as a tactical approach in order to introduce structural changes in the target moiety that can be beneficial in improving potency, enhancing selectivity, and altering physical properties, reducing or redirecting metabolisms, eliminating or modifying toxicophores . In the present study, we have employed the concept of bioisosterism with the aim of addressing ROS-mediated acetaminophen toxicity.…”

“…14 In the contemporary practice of drug design, the concept of bioisosteric replacement has been adopted as a tactical approach in order to introduce structural changes in the target moiety that can be beneficial in improving potency, enhancing selectivity, and altering physical properties, reducing or redirecting metabolisms, eliminating or modifying toxicophores. 15 In the present study, we have employed the concept of bioisosterism with the aim of addressing ROS-mediated acetaminophen toxicity. For the said purpose we utilized a 1,2,3-triazole scaffold to create AP−triazole conjugated pharmacophores with increased efficacy and no toxicity.…”

Attaching Metal-Containing Moieties to Lactam Antibiotics: The Case of Penicillin and Cephalosporin

“…The synthesis of azide 17a, 9 has been carried out under the following conditions: freshly distilled NEt3 (1.40 mL, 9.82 mmol, 2.0 eq) was added dropwise to a suspension of the tosylate salt 16a (2.35 g, 4.91 mmol, 1.0 eq) in anhydrous CH2Cl2 (90 mL), under an argon atmosphere, and stirred at room temperature for 45 min. Next, NfN3…”