Synthesis, Characterization, Biological Screening, ADME and Molecular Docking Studies of 2-Phenyl Quinoline-4-Carboxamide Derivatives

Abstract

In this work, some 2-phenyl quinoline-4-carboxamide derivatives (5a-j) were synthesized via base catalyzed Pfitzinger reaction of isatin and acetophenone followed by C-N coupling reaction using POCl3 and assessed them for their in vitro antimicrobial and anticancer activity. The structure of newly synthesized compound were established by FT-IR, 1H & 13C NMR and Mass spectrometric analysis. The synthesized carboxamides were subjected to preliminary in vitro antibacterial activity as well as for antifungal activity. Results of antibacterial activity were compared with standard antibacterial (ciprofloxocin) and antifungal (fluconozole). Among the tested compounds, 5d, 5f and 5h exhibited promising activity with zone of inhibition ranging from 10 to 25 mm. Further, the anticancer activity determined using MTT assay against two cancer cell lines. Compounds 5b, 5d, 5f and 5h showed good anticancer activity among all the other derivatives. In order to correlate the in vitro results, in silico ADME and Molecular docking studies were carried out for (5a-j). ADME properties results showed that all the compounds obey rule of Five rule except 5a, 5e and 5g compound. Molecular docking studies of the synthesized compounds showed good binding affinity through hydrogen bond interactions with key residues on active sites as well as neighboring residues within the active site of chosen target proteins viz. antibacterial, antifungal and anticancer. Comparison of both results of in silico as well as in vitro investigation suggests that the synthesized compounds may act as potential antimicrobial as well as anticancer agents.

3D-QSAR Modeling on 2-Pyrimidine Carbohydrazides as Utrophin Modulators for the Treatment of Duchenne Muscular Dystrophy by Combining CoMFA, CoMSIA, and Molecular Docking Studies

“…The guidelines outline molecular characteristics that are critical to a drug’s pharmacokinetics, that is, how it is absorbed, distributed, metabolized, and excreted in the human body in the “ADME” section. The rule, however, is unable to determine if a substance is pharmacologically active. , Using the Swiss ADME web server (), the physical properties and ADME parameters of the designed compounds were calculated. , Based on these findings summarized in Table , except for two compounds (D1 and D4) that only violated the molecular weight guideline, the rest of the designed compounds obeyed Lipinski’s rule of five. As can be seen in Table , all the compounds designed in this work included the properties of a drug and showed very good synthetic accessibility.…”

“…The rule, however, is unable to determine if a substance is pharmacologically active. 27,28 Using the Swiss ADME web server (http://www.swissadme.ch/), the physical properties and ADME parameters of the designed compounds were calculated. 29,30 Based on these findings summarized in Table 3, except for two compounds (D1 and D4) that only violated the molecular weight guideline, the rest of the designed compounds obeyed Lipinski's rule of five.…”

Unravelling the synthetic and therapeutic aspects of five, six and fused heterocycles using Vilsmeier–Haack reagent

“…In 2020, Shetty et al 54 produced 1,3-diphenylpyrazole-4-carboxaldehyde from phenylhydrazone using V. H. reagent (DMF-POCl 3 ) in ice-bath followed by stirring the reaction mixture at 70 to 80 °C for 6 hours, in good yield. This carbaldehyde was used as an excellent precursor for the synthesis of Schiff base by reacting with primary amines.…”

Comprehensive Review on Schiff Base Heterocyclic Moiety Conjugates: Synthesis, Reactions and Diverse Applications

“…E)4-nitrobenzylidene)-4-((E)-(4-methoxyphenyl) diazenyl)-1-phenyl-pyrazole-5-amine 24 was combined with 4-nitro benzaldehyde 25 and respectively, to create the pyrazole Schiff base derivative 26. This reaction took place in refluxed THF[14].…”