Activity against Mycobacterium tuberculosis of a new class of spirooxindolopyrrolidine embedded chromanone hybrid heterocycles.

A new class of structurally intriguing heterocycles embedded with spiropyrrolidine, oxindole and chromanones was prepared by regio- and stereoselectively in quantitative yields using an intermolecular tandem cycloaddition protocol. The compounds synthesized were assayed for their anti-mycobacterial activity against Mycobacterium tuberculosis (Mtb) H37Rv and isoniazid-resistant (katG and inhA promoter mutations) clinical Mtb isolates. Four compounds exhibited significant antimycobacterial activity against Mtb strains tested. In particular, a compound possessing a fluorine substituted derivative displayed potent activity at 0.39 µg mL-1 against H37Rv, while it showed 0.09 µg mL-1 and 0.19 µg mL-1 activity against inhA promoter and katG mutation isolates, respectively. A molecular docking study was conducted with the potent compound, which showed results that were consistent with the in vitro experiments.

Chemical Characterization and Chemotaxonomic Significance of Essential Oil Constituents of Matricaria aurea Grown in Two Different Agro-Climatic Conditions.

A comprehensive study on chemical characterization of essential oil (EO) constituents of a rarely explored plant species (Matricaria aurea) of the Asteraceae family grown in Saudi Arabia and Jordan was carried out. Analyses were conducted employing gas chromatographic approaches such as GC-MS, GC-FID, and Co-GC, as well as RT, LRI determination, and database and literature comparisons, on two diverse stationary phase columns, which led to the identification of a total of 135 constituents from both EOs. Oxygenated sesquiterpenes were found to be the most predominant chemical class of Saudi M. aurea EOs, in which α-bisabolol (27.8%), γ-gurjunenepoxide (21.7%), (E, E)-α-farnesene (16.3%), and cis-spiroether (7.5%) were present as major components. In contrast, the most dominant chemical class of Jordanian M. aurea oil was found to be sesquiterpene hydrocarbons, where (E, E)-α-farnesene (50.2%), γ-gurjunenepoxide (8.5%), (E)-ß-farnesene (8.1%), and (Z, E)-α-farnesene (4.4%) were detected as chief constituents. It is interesting to mention here that Saudi and Jordanian M. aurea EOs showed quite interesting chemical compositions and were found to have different chemotypes when compared to previously reported M. aurea EO compositions.

Biodegradation of neonicotinoid insecticide acetamiprid by earthworm gut bacteria Brucella intermedium PDB13 and its ecotoxicity.

Extensive use of neonicotinoid insecticides in recent decade had contaminated water and soil systems and poses serious environmental and health risk. Microbial degradation of toxic contaminants in the environment has been established as a sustainable tool towards its remediation. Under this context, the present study focused on the biodegradation of neonicotinoid insecticide acetamiprid, by bacterial strain Brucella intermedia PDB13 isolated from the gut of the acetamiprid exposed earthworms. To enhance acetamiprid biodegradation, suitable parameters such as pH, temperature, inoculum size and acetamiprid concentration range were optimised using Response Surface Methodology (RSM). The experimental results showed that the Brucella intermedium PDB13 can tolerate and degrade relatively high concentrations of acetamiprid (50 - 350 mg L-1). The results confirmed that maximum degradation of about 89.72% was achieved under optimized conditions. Further, confirmation of acetamiprid biodegradation was assessed through the occurrence of its degraded metabolites through HPLC, FTIR, and LCMS analysis. Based on this analysis, possible acetamiprid biodegradation pathway by Brucella intermedia PDB13 was proposed. Additionally, cytotoxicity, earthworm acute toxicity, and zebrafish embryo toxicity studies were also performed to assess the toxicity variations between the parent compound and its metabolites. The acetamiprid treated group resulted in cytotoxic effects apparently, with the increase in aberrant cells frequency (22.5 ± 3.3), when compared with its metabolites (2.3 ± 4.3) and control (1.9 ± 5.6) respectively. All these results evidently reported the degradation potential of Brucella intermedia PDB13, thereby establishing the scope for further advanced biodegradation studies towards mitigating the pesticide pollution.

Ultrasonic assisted synthesis of RGO supported HoVO4-ZnO nanocomposites, their enhanced photocatalytic activities and Rhodamine B degradation.

The RGO-supported HoVO4-ZnO nanocomposite was synthesized using the ultra sonication process. X-ray diffraction patterns, Field emission scanning electron microscopy, high resolution transmission electron microscopy, Diffractive Reflectance spectroscopy, and photoluminescence spectroscopy were employed to examine the heterostructured photocatalyst in this research study. The photocatalytic efficiency of the RGO-supported HoVO4-ZnO nanoparticles, under UV light irradiation, in the degradation of Rhodamine-B dye was investigated. Undoped ZnO, bare HoVO4, and HoVO4 -ZnO, degraded at 55.6, 57.5, and 74.33 percent in 45 min, respectively. This new RGO coupled HoVO4-ZnO exhibits enhanced photocatalytic efficiency compared to the bare ZnO and HoVO4-ZnO nanocomposite.

Antimicrobial activities of novel class of dispirooxindolopyrrolidine grafted indanedione hybrid heterocycles against carbapenemase producing Klebsiella pneumoniae (CKP).

BACKGROUND: Aggressive antimicrobial infections together with an increasing in resistance to antimicrobial medications cause a threat to immunocompromised individual. In this context, spiro compounds play an important role in drug discovery research due to their diverse biological activities including antimicrobial activity which is well documented in literature, because of their unique structural properties allow for easy interaction with the target enzyme of the biological system. This biological precedent encouraged us to design and synthesis of novel dispirooxindolopyrrolidine hybrid heterocycles via multicomponent cycloaddition protocol. MATERIALS AND METHODS: Novel class of dispirooxindolopyrrolidine hybrid heterocycles has been synthesized by multicomponent 1,3-dipolar cycloaddition methodology and the structure of the products was determined through spectroscopic analysis. The synthesized organic compounds were evaluated for their antimicrobial activities using sensitivity test with standard agar well diffusion method. RESULTS: The synthesized new class of dispiropyrrolidine embedded indandione hybrids showed significant antimicrobial activity against carbapenemase producing Klebsiella pneumoniae (CKPs) isolated from hospital patients. Compound that possessing chlorine substituted on the aryl ring exhibited more potent antimicrobial activities and the zone of inhibitions was observed between 7.00 ± 0.09 and 18.40 ± 0.70 mm. The MIC value of compound 4b was 0.030 mg/mL against tested CKP. CONCLUSION: A new class of dispiropyrrolidine heterocyclic hybrids were synthesized in good to excellent yield employing multicomponent 1,3-dipolar cycloaddition strategy. Among them, compounds bearing 4-chloro substituted on the aryl ring exhibited notable activity just equal to the standard drug, ciprofloxacin. Future studies are needed to elucidate the pharmacological properties of new compounds that were synthesized in our laboratory for the novel therapeutic development.

Regio- and diastereoselective synthesis of spiropyrroloquinoxaline grafted indole heterocyclic hybrids and evaluation of their anti-Mycobacterium tuberculosis activity.

An efficient and eco compatible approach for the regio- and stereoselective synthesis of structurally diverse novel hybrid heterocycles comprising spiropyrrolidine, indenoquinoxaline and indole structural units in excellent yields, has been achieved through a one-pot multicomponent process involving 1,3-dipolar cycloaddition as a key step. The 1,3-dipolar component is the azomethine ylide generated in situ from indenoquinoxaline and l-tryptophan and reacts with various substituted ß-nitrostyrenes affording the spiroheterocyclic hybrids. The ring system thus created possesses two C-C and three C-N bonds and four adjacent stereogenic carbons, one of which is quaternary and the reaction proceeded with full diastereomeric control. All the synthesized compounds were assayed for their in vitro activity against Mycobacterium tuberculosis H37Rv using MABA assay. Interestingly, the compound bearing a 2-fluoro substituent on the aryl ring displayed an equipotent activity (MIC 1.56 µg mL-1) to ethambutol against Mycobacterium tuberculosis H37Rv.