Prospects of Plant Derived Bioactive Compounds as Nanoparticles for Biotechnological Applications.

Nanoparticles bestow beneficial impacts on plants, specifically in increasing photosynthetic capacity and germination rate, pesticide delivery, managing pathogenicity and enhancing nutrient supply. The nanoparticles produced from the medicinal plant extracts are identified as an exceptional applicant in nanomedicine, cosmetics, and agriculture for the treatment of diseases as antimicrobial, antioxidant and anticancer agents, etc. Plant extracts actually have bioactive metabolites that provide therapeutic potential against a variety of diseases. Herein, we review the production of bioactive compounds from leaves, roots, seeds, flowers and stems. We further summarize the different methods for obtaining plant extracts and the green technologies for the synthesis of nanoparticles of plant derived bioactive compounds. Biotechnological aspects of these synthesized nanoparticles are also added here as highlights of this review. Overall, plant derived nanoparticles provide an alternative to conventional approaches for drug delivery as well and present exciting opportunities for future research on novel areas.

Malignance-restriction activity exhibited by bioactive compounds of selected actinobacteria as silver nanoparticles against A549 lung cancer cell lines.

This article deals with the antibacterial and anticancer potential of secondary metabolites produced by actinomycetes also reported as actinobacteria, Microbacterium proteolyticum (MN560041), and Streptomycetes rochei, where preliminary studies were done with the well diffusion method. These actinobacteria's silver nanoparticles were synthesized and characterized using transmission electron microscopy (TEM) and UV-Visible spectroscopy. Anticancer was measured using the MTT test, reactive oxygen species (ROS) generation measured with DCFDA, mitochondrial membrane potential (MMP) measurement, and DAPI fluorescence intensity activity was measured in treated and non-treated cancerous cells. The IC50 value for 5-FU (a), LA2(O) (b), LA2(R) (c), LA2(ON) (d), and LA2(RN) (e) was obtained at 3.91 µg/mL (52.73% cell viability), 56.12 µg/mL (52.35% cell viability), 44.90 µg/mL (52.3% cell viability), 3.45 µg/mL (50.25% cell viability), and 8.05 µg/mL (48.72% cell viability), respectively. TEM micrographs revealed discrete, well-separated AgNPs particles of size 7.88 ± 2 to 12.86 ± 0.24 nm. Gas chromatography-mass spectrometry was also performed to detect the compounds in bioactive metabolites where n-hexadecanoic acid was obtained as the most significant one. MTT test showed a substantial decline in A549 cell viability (up to 48.72%), 2.75-fold increase in ROS generation was noticed in comparison to untreated A549 lung cancer cells when measured with DCFDA. A total of 0.31-fold decrease in MMP and 1.74-fold increase in DAPI fluorescence intensity compared to untreated A549 lung cancer cells suggests that the synthesized nanoparticles promote apoptosis in cancerous cells. Our findings suggests that the secondary metabolites of M. proteolyticum and S. rochei in nanoparticle form can be used as a significant compound against lung cancers.

Visible-light promoted catalyst-free (VLCF) multi-component synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids: evaluation of in vitro anticancer activity, molecular docking, MD simulation and DFT studies.

A new and highly efficient visible-light-promoted catalyst free (VLCF) strategy for neat and clean synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids (6a-d) has been introduced. We have performed visible-light triggered 1,3-Dipolar cycloaddition reaction of maleimide (5a-d) with azomethine ylide generated in situ derived from tryptanthrin (3) and L-proline (4) to obtain desired products (6a-d) in good to excellent yield. Authentication and characterization of product was done using various spectroscopic techniques such as IR, 1H NMR, 13C NMR, Mass spectrometry and single crystal XRD analysis. To explain the reaction spontaneity, product stability, reactivity as well as possible mode of the interaction a quantum chemical investigation was performed and depicted through DFT studies. The synthesized compound 6a was also evaluated for anti-proliferative activity against a panel of five cancer cell lines (MCF-7, MDA-MB-231, HeLa, PC-3 and Ishikawa) and normal human embryonic kidney (HEK-293) cell line by using MTT assay. Compound 6a showed very good in vitro anti-proliferative activity (IC50  = 6.58-17.98 µM) against four cancer cell lines and no cytotoxicity against normal HEK-293. In order to evaluate the anticancer potential of compounds 6a-d, molecular docking was performed against wild type and mutant EGFR. The results suggest that all the compounds occupied the active site of both enzymes, with a strong binding energy (-10.2 to -11.5 kcal/mol). These results have been confirmed by molecular dynamics simulation by evaluating root mean square deviation (RMSD) and root mean square fluctuation (RMSF), along with principal component analysis (PCA).Communicated by Ramaswamy H. Sarma.

Purification and characterization of extracellular PHB depolymerase enzyme from Aeromonas caviae Kuk1-(34) and their biodegradation studies with polymer films.

PHB depolymerase enzymes are able to breakdown the PHB polymers and thereby get significant economic value in the bioplastics industry and for bioremediation as well. This study shows the purification of novel extracellular PHB depolymerase enzyme from Aeromonas caviae Kuk1-(34) using dialysis followed by gel filtration and HPLC. The purification fold and yield after HPLC were 45.92 and 27.04%, respectively. HPLC data showed a single peak with a retention time of 1.937 min. GC-MS analysis reveals the presence of three compounds, of which 1-Dodecanol was found to be most significant with 54.48% area and 8.623-min retention time (RT). The molecular weight of the purified enzyme was obtained as 35 kDa with Km and apparent Vmax values of 0.769 mg/mL and 1.89 U/mL, respectively. The enzyme was moderately active at an optimum temperature of 35 °C and at pH 8.0. The stability was detected at pH 7.0-9.0 and 35-45 °C. Complete activity loss was observed with EDTA, SDS, Tween-20 at 5 mM and with 0.1% Triton X 100. A biodegradation study of commercially available biodegradable polymer films was carried out in a liquid medium and in soil separately with pure microbial culture and with purified enzyme for 7, 14, 28, and 49 consecutive days. In a liquid medium, with a pure strain of Aeromonas caviae Kuk1-(34), the maximum degradation (89%) was achieved on the PHB film, while no changes were observed with other polymer films. With purified enzyme in the soil, 71% degradation of the PHB film was noticed, and it was only 18% in the liquid medium. All such weight analysis were confirmed by SEM images where several holes, pits, grooves, crest, and surface roughness are clearly observed. Our results demonstrated the potential utility of Aeromonas caviae Kuk1-(34) as a source of extracellular PHB depolymerase capable of degrading PHB under a wide range of natural/ lab conditions.

Visible Light-Promoted Green and Sustainable Approach for One-Pot Synthesis of 4,4'-(Arylmethylene)bis(1H-pyrazol-5-ols), In Vitro Anticancer Activity, and Molecular Docking with Covid-19 Mpro.

A visible light-promoted, efficient, green, and sustainable strategy has been adopted to unlatch a new pathway toward the synthesis of a library of medicinally important 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols) moieties using substituted aromatic aldehydes and sterically hindered 3-methyl-1-phenyl-2-pyrazoline-5-one in excellent yield. This reaction shows high functional group tolerance and provides a cost-effective and catalyst-free protocol for the quick synthesis of biologically active compounds from readily available substrates. Synthesized compounds were characterized by spectroscopic techniques such as IR, 1HNMR, 13CNMR, and single-crystal XRD analysis. All the synthesized compounds were evaluated for their antiproliferative activities against a panel of five different human cancer cell lines and compared with Tamoxifen using MTT assay. Compound 3m exhibited maximum antiproliferative activity and was found to be more active as compared to Tamoxifen against both the MCF-7 and MDA-MB-231 cell lines with an IC50 of 5.45 and 9.47 µM, respectively. A molecular docking study with respect to COVID-19 main protease (Mpro) (PDB ID: 6LU7) has also been carried out which shows comparatively high binding affinity of compounds 3f and 3g (-8.3 and -8.8 Kcal/mole, respectively) than few reported drugs such as ritonavir, remdesivir, ribacvirin, favipiravir, hydroxychloroquine, chloroquine, and olsaltamivir. Hence, it reveals the possibility of these compounds to be used as effective COVID-19 inhibitors.

Photodegradation and In Silico Molecular Docking Study of a Diuretic Drug: Clopamide.

Clopamide (CPD, 1) is a piperidine and sulfamoylbenzamide-based diuretic drug and a potential photosensitizing sulfonamide; its phototransformation was investigated using N,N-dimethylaniline (DMA) as an electron donor and 1,4-dicyanonaphthalene (DCN) as an electron acceptor in an immersion-well-type photochemical reactor fitted with a medium-pressure mercury vapor lamp (450 W). Photodegradation of the drug Clopamide resulted in two significant products via photoinduced electron transfer. Structures of these products were deduced from their 1H NMR, 13C NMR, mass, and IR spectra. The photoproducts are 2- choloro-5-((2,6-dimethylpiperidin-1-yl)carbamoyl)benzenesulfonic acid (2) and 4-hydroxy-N-(2,6-dimethyl-1-piperidyl)-3-sulfamoyl benzamide (3). In addition to this, the comparative antioxidant potentials of the parent drug and its photoproducts were investigated using in silico molecular docking against tyrosinase in order to better understand the in vivo relevance of pharmacological action of the drug as a result of light-drug interactions. UV light has been observed to modify substituents on the benzene ring, hence loss of biological activity at the time of storage and in vivo cannot be ruled out. This suggests that Clopamide users should avoid light (natural or artificial) exposure to prevent from drug-induced photosensitivity.

Isolation and optimization of extracellular PHB depolymerase producer Aeromonas caviae Kuk1-(34) for sustainable solid waste management of biodegradable polymers.

Bioplastics, synthesized by several microbes, accumulates inside cells under stress conditions as a storage material. Several microbial enzymes play a crucial role in their degradation. This research was carried to test the biodegradability of poly-ß-hydroxybutyrate (PHB) utilizing PHB depolymerase, produced by bacteria isolated from sewage waste soil samples. Potent PHB degrader was screened based on the highest zone of hydrolysis followed by PHB depolymerase activity. Soil burial method was employed to check their degradation ability at different incubation periods of 15, 30, and 45 days at 37±2°C, pH 7.0 at 60% moisture with 1% microbial inoculum of Aeromonas caviae Kuk1-(34) (MN414252). Without optimized conditions, 85.76% of the total weight of the PHB film was degraded after 45 days. This degradation was confirmed with Fourier-transform infrared spectroscopy (FTIR) and Scanning electron microscope (SEM) analysis. The presence of bacterial colonies on the surface of the degraded film, along with crest, holes, surface erosion, and roughness, were visible. Media optimization was carried out in statistical mode using Plackett Burman (PB) and Central Composite Design (CCD) of Response Surface Methodology (RSM) by considering ten different factors. Analysis of Variance (ANOVA), Pareto chart, response surface plots, and F-value of 3.82 implies that the above statistical model was significant. The best production of PHB depolymerase enzyme (14.98 U/mL) was observed when strain Kuk1-(34) was grown in a media containing 0.1% PHB, K2HPO4 (1.6 gm/L) at 27 ℃ for seven days. Exploiting these statistically optimized conditions, the culture was found to be a suitable candidate for the management of solid waste, where 94.4% of the total weight of the PHB film was degraded after 45 days of incubation.

Electron Transfer-Mediated Photodegradation of Phototoxic Antipsychotic Drug Quetiapine.

Quetiapine (QTP) (1), a psychotropic agent belonging to a chemical class, dibenzothiazepine derivatives, is photosensitive and photolabile. Its photochemistry was studied in the presence of an electron donor N,N-dimethylaniline (DMA) and an electron acceptor 1,4-dicyanobenzene (DCB) under anaerobic conditions. This resulted in photoinduced electron transfer-mediated transformation of drug QTP. Irradiation of Quetiapine (QTP, 1) in the presence of electron donor N,N-dimethylaniline (DMA) under anaerobic conditions in a photochemical reactor afforded one major photoproduct 2 when irradiation of QTP (1) was carried out in the presence of electron acceptor 1,4-dicyanobenzene (DCB) under similar conditions; it afforded 3 as a major photoproduct. These photoproducts were isolated and characterized on the basis of their spectral (IR, UV, 1H NMR, 13C NMR, and mass spectra) studies. The photophysical properties of Quetiapine were also determined in several solvents to investigate the relevance of the molecular structure in their photophysics and consequently in their photochemistry.

Sol-gel synthesis of thorn-like ZnO nanoparticles endorsing mechanical stirring effect and their antimicrobial activities: Potential role as nano-antibiotics.

The effect of mechanical stirring on sol-gel synthesis of thorn-like ZnO nanoparticles (ZnO-NPs) and antimicrobial activities is successfully reported in this study. The in-house synthesized nanoparticles were characterized by XRD, SEM, TEM, FTIR, TGA, DSC and UV-visible spectroscopy. The X-Ray Diffraction analysis revealed the wurtzite crystal lattice for ZnO-NPs with no impurities present. The diametric measurements of the synthesized thorn-like ZnO-NPs (morphology assessed by SEM) were well accounted to be less than 50 nm with the help of TEM. Relative decrease in aspect ratio was observed on increasing the agitation speed. The UV-visible spectroscopy showed the absorption peaks of the ZnO-NPs existed in both UVA and UVB region. A hypsochromic shift in λmax was observed when stirring pace was increased from 500 rpm to 2000 rpm. The FTIR spectroscopy showed the absorption bands of the stretching modes of Zn-O between 500 cm(-1) to 525 cm(-1). The Thermal analysis studies revealed better stability for ZnO-NPs prepared at 2000 rpm (ZnO-2000 rpm). TGA revealed the weight loss between two main temperatures ranges viz. around (90 °C-120 °C) and (240 °C-280 °C). Finally, the effect of ZnO-NPs prepared at different stirring conditions on the growth of Gram-positive (Bacillus subtilis), Gram-negative (Escherichia coli) bacteria and a fungi (Candida albicans) were examined; which showed good antibacterial as well as antifungal properties. These findings introduce a simple, inexpensive process to synthesize ZnO-NPs using conventional methods without the use of sophisticated equipments and its application as a potent nano-antibiotic.

Molecular mechanisms of drug photodegradation and photosensitization.

Drug-induced photosensitivity of the skin is drawing increasing attention. In past few decades, photosensitivity has been reported with an array of drugs, and is now recognized as a noteworthy medical problem by clinicians, regulatory authorities and pharmaceutical industry. The photosensitivity is of two types i.e., phototoxicity and photoallergy. Phototoxic disorders have a high incidence, whereas photoallergic reactions are much less frequent in human population. Several hundred substances, chemicals, or drugs may invoke phototoxic and photoallergic reactions. In order to avoid photosensitive reactions, it is essential to understand the mechanism behind the photosensitizing properties of such substances before these drugs are introduced in clinical settings. Photosensitization is inter-related to photochemical reaction, through the knowledge of which the photosensitivity of a drug can be anticipated. This review highlights the current research status on photosensitizing drugs and its correlation to phototoxicity. Different mechanisms of photodegradation of photolabile drugs have also been discussed.