Facile Synthesis of 6-Phenyl-6h-chromeno [4, 3-b] Quinoline Derivatives using NaHSO4@SiO2 Re-usable Catalyst and Their Antibacterial Activity Study Correlated by Molecular Docking Studies

Abstract

<jats:sec> <jats:title>Background:</jats:title> <jats:p>Heterocyclic compounds containing heteroatoms (O, N and S) as part of five or six-membered cyclic moieties exhibited various potential applications, such as pharmaceutical drugs, agrochemical products and organic materials. Among many known heterocyclic moieties, quinoline and its derivatives are one of the privileged scaffolds found in many natural products. In general, quinoline derivatives could be prepared by utilizing ortho-substituted anilines and carbonyl compounds containing a reactive α-methylene group of well-known reaction routes like Friedlander synthesis, Niemantowski synthesis and Pfitzinger synthesis. Moreover, polysubstituted quinolones and their derivatives also had shown considerable interest in the fields of organic and pharmaceutical chemistry in recent years.</jats:p> </jats:sec> <jats:sec> <jats:title>Objective:</jats:title> <jats:p>The main objective of our research work is towards the design and synthesis of divergent biological-oriented, proactive analogues with potential pharmacological value inspired by the anti-tubercular activity of 2-phenylquinoline analogues. In this study, we have been interested in the design and synthesis of bioactive, 2, 4-diphenyl, 8-arylated quinoline analogues.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>6-phenyl-6h-chromeno [4, 3-b] quinoline derivatives were synthesized from 4-chloro-2- phenyl-2H-chromene-3-carbaldehyde and various substituted aromatic anilines as starting materials using sodium bisulfate embedded SiO2 re-usable catalyst. All these fifteen new compound structures confirmed by spectral data 1H &amp; 13C NMR, Mass, CHN analysis etc. Furthermore, all these new compounds antibacterial activity strains recorded using the paper disc method. The compound molecular structures were designed using molecular docking study by utilizing the crystallographic parameters of S. Areus Murb protein.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p> A series of fifteen new quinoline derivatives synthesized in moderate to good yields using sodium bisulfate embedded SiO2 re-usable catalyst. The molecular structures of these newly synthesized compounds elucidated by the combination of spectral data along with the elemental analysis. These compounds antibacterial activity study have shown moderate to good activity against, Escherichia coli (Gram-negative) and Staphylococcus aureus (gram-positive) organisms. These antibacterial activity results were also a very good correlation with molecular docking studies.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>In this study, fifteen new quinoline derivatives synthesized and structures confirmed by spectral data. In fact, all the compounds have shown moderate to good antibacterial activity. In general, the compounds containing the electron donor group at R1 position (R1 = OMe) and the acceptor group at R2 positions (R2 = F or Cl) had shown good antibacterial activity. These antibacterial activity results were also a very good correlation with molecular docking studies showing strong binding energies with the highest value being, -12.45 Kcal mol-1 with S. aureus MurB receptor.</jats:p> </jats:sec>

Design and Synthesis of “Chloropicolinate Amides and Urea Derivatives” as Novel Inhibitors for Mycobacterium tuberculosis

“…However, five compounds, 16 (6.96 μM), 19 (6.98 μM), 28 (7.00 μM), 22 (7.86 μM), and 10 (7.90 μM), showed good MIC values that are prominently exhibiting in vitro potency close to isoniazid and higher than ethambutol. Among the other compounds, 13,14,17,18,20,21,24,29,30,31, and 32 are also promising candidates based on their MIC values reported in Table 2 for the inhibitors of Mtb.…”

“…With this strategy, we designed 30 new heterocyclic scaffolds that could be synthesized by treating methyl 4-amino-6-(2-aminophenyl)-3-chloropyridine-2-carboxylate with different acid chloride, urea, and thiourea moieties. Besides, one of the major research area for our group is to design and synthesize a new heterocyclic scaffold containing compounds for novel biological activity and material applications. ,− …”

Sacubitril‐Based Urea and Thiourea Derivatives as Novel Inhibitors for Anti‐Tubercular against Dormant Tuberculosis

“…The new approach to drug discovery is the incorporation of various biologically active molecules in a single hybrid framework may allow changes in the biological properties of the hybrid molecule when compared to the parent molecule [27] . In continuation of our ongoing interest, [15,16,23–25] in the present study, we are amalgamating the urea and thiourea precursors with pharmaceutical important Sacubitril moiety and further explored their anti‐TB activity.…”

“…Similarly, the thiourea derivative such as thiocarlide has exhibited potent antituberculosis activity against Mtb H37Rv through the inhibition of the mycolic acid synthesis [20] . Apart from this, urea and thiourea based heterocyclic derivatives display anticancer, antimicrobial, anthelmintic and insecticidal activities [21–26] . The new approach to drug discovery is the incorporation of various biologically active molecules in a single hybrid framework may allow changes in the biological properties of the hybrid molecule when compared to the parent molecule [27] .…”