Metal‐Free Based Domino Approach to Pyrano‐Fused‐Pyrido[3,2,1‐jk]carbazolones: Antibacterial and Molecular Docking Studies

Abstract

A facile, metal-free based one-pot annulation reaction of several Morita-Baylis-Hillman acetates of MVK/acrylate with 4hydroxy-6H-pyrido[3,2,1-jk]carbazol-6-one as C/O-1,3-binucleophile promoted by DABCO as an organobase in 2-MeTHF at room temperature is reported. This environmentally benign method delivers a family of pyrano-fused pyridocarbazolones in high yields with medium to good diastereoselectivities under mild conditions. Antibacterial studies showed that attaching carboxylate group on pyran ring of pyrano-fused pyridocarbazolones has shown better activities (MIC up to � 6.25 μg/mL) as compared to acetyl one. Interestingly, incorporation of several substituents namely CF 3 , NO 2 , MeO, F, Cl and Br on the aryl rings of pyridocarbazolones carboxylates sharply enhanced the antibacterial activities which make them more potent or equipotent than commercial antibiotic ofloxacin. Furthermore, in silico docking studies indicated that MolDock scores of transisomers with E. coli protein are in general higher than cisisomers which are in good agreement with their observed in vitro antibacterial activities. Results and DiscussionWe started our initial reaction by involving 4-hydroxy-6Hpyrido[3,2,1-jk]carbazol-6-one (1) and MBH acetate of methyl vinyl ketone (MVK) 2 a as model substrates in CH 2 Cl 2 in the [a] Dr.

Interactions of Co, Cu, and non-metal phthalocyanines with external structures of SARS-CoV-2 using docking and molecular dynamics

“…1 ) with the surface structures of SARS-CoV-2 (Fig. 2 ); we used Molegro Virtual Docker 4.2 (MVD) 48 , 49 , which presented satisfactory results, as its scoring function can recognize metals 48 , 50 . The Molegro scoring function 51 applies to all heavy atoms in the ligand and protein, including the cofactor atoms 52 , 53 .…”

Prediction of antifungal activity, cytotoxicity risks and molecular docking against <em>Malassezia furfur</em> of constituents of citronella essential oil (<em>Cymbopogon winterianus</em>)

“…After that, molecular docking was performed in the software Molegro Virtual Docker 6.0 (MVD) [5], using the crystallographic protein published in PDB with ID 1SJX [6], corresponding to the three-dimensional structure of a llama VHH domain OE7 binding the M. furfur cell wall protein.…”

(±)‐cis‐4a‐alkyl‐1,3,4,4a,9,9a‐hexahydro‐2H‐carbazol‐2‐ones by domino nitro reduction‐aza‐Michael addition to enones

“…Yield: 0.98 g (4.70 mmol, 94%) as a yellow oil; IR: 3366, 1523, 1354 cm À1 ; 1 H NMR (400 MHz, CDCl 3 ): δ 7.71 (d, J = 8.1 Hz, 1H), 7.57 (t, J = 7.9 Hz, 1H), 7.48 (d, J = 7.9 Hz, 1H), 7.35 (t, J = 7.9 Hz, 1H), 3.84 (m, 1H), 3.76 (m, 1H), 3.37 (m, 1H), 1.76 (overlapping m and br s, 2H), 1.62 (m, 1H), 1.23 (m, 2H), 0.86 (t. J = 7. 3 A 250-ml [17], three-necked, round-bottomed flask equipped with a mechanical stirrer, a condenser, and a septum was charged with dichloromethane (20 ml, DCM) and oxalyl chloride (0.76 g, 0.51 ml, 6.0 mmol) and was cooled to À78 C. To this solution was added dropwise dimethyl sulfoxide (0.94 g, 0.79 ml, 12.0 mmol) in DCM (2 ml), and the mixture was stirred a À78 C for 15 min. The 2-(2-nitrophenyl)-1-alkanols (5, 3.0 mmol) in DCM (2 ml) was then added dropwise, and the mixture was stirred for 30 min.…”

“…Carbazoles and carbazolones are important targets in medicinal chemistry. Carbazoles have recently been reviewed as anticancer agents [1], and are core structures in compounds examined as antibacterials [2,3] and as allosteric modulators at muscarinic acetylcholine receptors [4]. Additionally, 1,2,3,9-tetra hydrocarbazol-4-ones have been investigated as anti psychotics [5], antihypertensives [6], and anticancer drugs [7,8].…”