Synergistic antimicrobial activity, MD simulation studies and crystal structure of natural alcohol motif containing novel substituted cinnamates.

A series of natural alcohols motif containing novel substituted cinnamates were developed and screened against five bacterial strains namely, Enterococcus faecal (E. faecalis), Escherichia coli (E. coli), Bacillus subtilis (B. subtilis), Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumonieae (K. pneumonieae). Among all cinnamates, YS17 was identified with 100% bacterial growth inhibition across the panel, except in E. faecalis with MIC values of 0.25 mg/mL against B. subtilis and P. aeruginosa whereas 0.125, 0.5 and 1 mg/mL against E. coli, K. pneumonieae and E. faecalis, respectively. The growth inhibitory property of YS17 was further validated by disk diffusion, synergistic study and in vitro toxicity assays. Interestingly, YS17 exhibits synergistic effect in combination with the standard drug Ampicillin (AMP). The single crystal structure analysis of YS4 and YS6 was also performed which reconfirmed their proposed structures. Molecular docking visualized significant non-covalent interactions between E. coli MetAP and YS17 and the structural and conformational changes were further analysed using MD simulation studies. Overall, the study provided a suitable core for further synthetic alterations for their optimization as an antibacterial agent. Communicated by Ramaswamy H. Sarma.

Correction: Aryl glyoxal: a prime synthetic equivalent for multicomponent reactions in the designing of oxygen heterocycles.

[This corrects the article DOI: 10.1039/D2RA08315A.].

Aryl glyoxal: a prime synthetic equivalent for multicomponent reactions in the designing of oxygen heterocycles.

The category of bifunctional building blocks overrides many others because of their fascinating wide applicability in synthetic chemistry. Aryl glyoxal is one of the key molecules that has been extensively used in heterocyclic chemistry to afford nearly all types of five- and six-membered heterocycles, which are the structural constituents of many natural products. The multicomponent reaction is a practical strategy to utilize this wonderful moiety with different types of starting materials to obtain numerous diverse oxygen heterocycles. This review covers the advancement of aryl glyoxal as a prime synthetic equivalent in recent years for the synthesis of oxygen heterocycles.

Design, Synthesis, and Biological Evaluation of Novel Fused Spiro-4H-Pyran Derivatives as Bacterial Biofilm Disruptor.

This study aims to synthesize novel fused spiro-4H-pyran derivatives under green conditions to develop agents having antimicrobial activity. The synthesized compounds were initially screened for in vitro antibacterial activity against two Gram-positive and three Gram-negative bacterial strains, and all the compounds exhibited moderate to potent antibacterial activity. However, compound 4l showed significant inhibition toward all the bacterial strains, particularly against Streptococcus pneumoniae and Escherichia coli with minimum inhibitory concentration values of 125 µg/mL for each. The toxicity studies of selected compounds (4c, 4e, 4l, and 4m) using human red blood cells as well as human embryonic kidney (HEK-293) cells showed nontoxic behavior at desired concentration. Growth kinetic and time-kill curve studies of 4l against S. pneumoniae and E. coli supported its bactericidal nature. Interestingly, compound 4l showed a synergistic effect when used in combination with ciprofloxacin against selected strains. Biofilm formation in the presence of a lead compound, as assessed by XTT assay, showed complete disruption of the bacterial biofilm visualized by scanning electron microscopy. Overall, the findings suggest 4l to be considered as a promising lead for further development as an antibacterial agent.

Nitroketene N,S-acetals: synergistic building blocks for the synthesis of heterocycles.

The development of novel heterocyclic compounds from simple and easily accessible starting components is of significant importance in medicinal chemistry. Due to the presence of active chromophores and potent pharmacological activities, nitroketene N,S-acetals have emerged as a fascinating building block in organic synthesis. The synergistic skeleton of these acetals and the presence of electron-donating as well as electron-withdrawing groups lead to the generation of distinctive structural features and are highly useful for building diverse heterocyclic rings. This review highlights the preparation of different nitroketene N,S-acetals and their applications in the synthesis of diverse heterocyclic compounds.

A catalyst- and solvent-free protocol for the sustainable synthesis of fused 4H-pyran derivatives.

An efficient and cost-effective method was developed for the synthesis of two kinds of fused 4H-pyran derivatives, namely, dihydropyrano[2,3-c]pyrazole 4 and pyrano[3,2-c]chromenone 6. The reactions of 3-methyl-1-phenyl-5-pyrazolone/4-hydroxycoumarin with aromatic aldehydes and (E)-N-methyl-1-(methylthio)-2-nitroethenamine (NMSM), involving the Knoevenagel, Michael-addition, O-cyclization and elimination reactions under thermal heating, afforded the desired products. The synthesized compounds were characterized by standard spectroscopic techniques. Further, the structures of pyrazole-fused 4H-pyran 4a and coumarin-fused 4H-pyran 6b were confirmed by single-crystal XRD analysis. The short reaction time, good-to-excellent yields, elimination of the use of expensive, metallic and toxic catalysts or hazardous organic solvents and high atom-economy are some noteworthy features of this protocol.

VO(acac)(2)/H(2)O(2)/NaI: a mild and efficient combination for the cleavage of dithioacetal derivatives of sugars.

A wide variety of dithioacetal derivatives of sugars can be cleaved easily into the corresponding open-chain aldehydo sugars using an efficient combination of VO(acac)(2)/H(2)O(2)/NaI at 0-5°C. Some of the salient features of this protocol are mild reaction conditions, good yields, short reaction times, easy work-up procedures, and non-involvement of toxic chemicals.

Tetrabutylammonium tribromide (TBATB): a mild and efficient catalyst for O-isopropylidenation of carbohydrates.

A wide range of O-isopropylidene derivatives can be prepared from the sugars and their derivatives on reaction with acetone at room temperature by employing 2 mol% of tetrabutylammonium tribromide (TBATB) as a catalyst. Good yields, low catalyst loading, mild reaction conditions, and a non-aqueous workup procedure are some major advantages of this protocol.

Bromodimethylsulfonium bromide (BDMS) mediated dithioacetalization of carbohydrates under solvent-free conditions.

A variety of diethyl dithioacetals of sugars can be prepared in very good yields by the reaction of various monosaccharides with ethanethiol in the presence of 3 mol% bromodimethylsulfonium bromide (BDMS) at 0-5°C. Similarly, dipropyl dithioacetal derivatives can also be obtained in good yields using propanethiol under identical reaction conditions. These dithioacetal derivatives were characterized by per-O-acetylation using silica gel-supported perchloric acid. The significant features of the present protocol are good-to-excellent yields, mild, clean, and solvent-free reaction conditions. This method is extremely suitable for the large-scale preparation of dithioacetal derivatives of various sugars.