Development of piperazine-1-carbothioamide chitosan silver nanoparticles (P1C-Tit*CAgNPs) as a promising anti-inflammatory candidate: a molecular docking validation

Abstract

Natural products are important leads in drug discovery. The search for effective plant-derived agents or their synthetic analogues has continued to be of interest to biologists and chemists for a long time. Herein, we have synthesized a novel compound, P1C, and P1C-Tit*CAgNPs from chitosan; P1C is a precursor and an anti-inflammatory candidate, which has been validated by molecular docking studies. The synthesized P1C-Tit*CAgNPs showed monodisperse, spherical, and cationic nature and antioxidant properties, protecting destabilization of the erythrocyte membrane by the azo compound 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH); the involvement of NPs as a protective agent for biomolecules, such as DNA and protein, followed by the treatment of NPs with AAPH was confirmed. The inhibition of cellular damage and leakage of cellular inflammatory agents was confirmed by AFM, SEM, TEM, SDS-PAGE, LDH, and PLA2 enzyme inhibition studies. The anti-inflammatory property of P1C was further validated by molecular docking studies and showed that, the P1C best pose aligned to PLA2 compared to standard drug. The significant anticancer property of P1C-Tit*CAgNPs was confirmed against MCF7, U373, and C6 cancer cell lines. Thus, the present study highlights the synthesized P1C in P1C-Tit*CAgNPs as a target PLA2-specific anti-inflammatory candidate, and further tuning of small and development-functionalized nanoparticles has a great future in medicine; hence, their clinical applications are warranted.

Synthetic approaches and pharmaceutical applications of chloro-containing molecules for drug discovery: A critical review

“…Compound 352 also showed potent phospholipase A2 (PLA2) enzyme inhibitory activity with IC 50 value of 18 mg/mL, which was much better than the reference drug Diclofenac (70 mg/mL) [119].…”

A Smart and Efficient One‐Pot Green Synthesis of Novel 1, 2, 3‐Triazolyl Pyrazoline‐/Indazolyl‐Carbothioamide Hybrids under Solvent‐Free Grinding Strategy at Room Temperature

“…On the other hand, substituted pyrazoline derivatives attract great attention due to their wide range of medicinal and pharmaceutical activities . Interestingly, pyrazoline/indazolyl‐carbothioamide motifs possess numerous biological activities such as antitubercular, antimicrobial, tricyclic necroptosis inhibitors, antifungal, antianalgesic, antiamoebic, anti‐inflammatory, antidepressant and anticonvulsant etc. (Figure ).…”