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The use of the green approach for nanoparticle synthesis yielded noticeable concern due to its eco-friendliness, cost-effectiveness, and reduced production of toxic chemicals. The current study was designed to formulate Zinc oxide nanoparticles (ZnO NPs) by using Fagonia cretica extracts, evaluating its phytochemical content, and different biological activities. Four different solvents; methanol (MeOH), n-Hexane (n–H), aqueous (Aq), and ethyl acetate (EA), had been utilized in the extracting method. ZnO NPs were successfully synthesized and characterized by UV–vis spectroscopy and scanning electron microscopy (SEM). The UV–vis spectra showed absorbance peaks between 350–400 nm range and SEM analysis revealed spherical morphology with particle sizes ranging from 65–80 nm. In phytochemical analysis, crude extracts exhibited the highest phytochemical content as they contain enriched secondary metabolites. n-hexane extract showed the highest phenolic contents while aqueous extracts showed the highest flavonoid content. Maximum free radicle scavenging activity was observed in NPs synthesized from ethyl-acetate extract with an IC50 value of 35.10 µg/ml. Significant antibacterial activity was exhibited by NPs polar solvents against K. pneumonae, E. coli, and B. subtilis. Polar solvents showed considerable antifungal potential against A. flavus and F. solani. NPs synthesized from nH extract showed potential cytotoxic activity with an LC50 value of 42.41 µg/ml against brine shrimps. A noteworthy antidiabetic activity was exhibited by nanoparticles synthesized from methanol extract i.e., 52.61 ± 0.36%. Significant bald zones were observed in nanoparticles synthesized from methanol extract rendering protein kinase inhibition. The present study highlights the significance of F. indica as a natural source for synthesizing functional nanoparticles with substantial antioxidant, antimicrobial, cytotoxic, protein kinase inhibitory, and antidiabetic properties. [ABSTRACT FROM AUTHOR]

A series of 18 biologically active C5‐arylated‐2‐isobutylthiazole derivatives that were synthesized by Pd‐NHC complexes [Pd(μ‐Cl)Cl (NHC)]2, NHC = SIXyl, 2), (LCl2Pd‐NHC, L = PPh3, 3), (LCl2Pd‐NHC, L = Py, 4), (LCl2Pd‐NHC, L = 3‐CHO‐Py, 5) catalyzed C‐H bond activation reactions. The catalytic activity of Pd‐NHC complexes was examined on the C‐H bond activation reaction of 2‐isobutylthiazole. All Pd‐NHC complexes were characterized by 1H nuclear magnetic resonance specroscopy (NMR), 13C NMR, fouirer transform infrared spektroscopy (FTIR), quadrupole‐time of flying‐liquit cromotagraphy/mass spektroscopy (Q‐TOF‐LC/MS), gas chromatography–mass spectrometry (GCMS), and melting point detection technique. The physicochemical properties, pharmacokinetics, and drug‐likeness were calculated by SwissADME. PkCSM database was used to calculate toxicities profile. All the products (6a–6s) were additionally assessed in vitro for their antidiabetic potential using α‐amylase and α‐glucosidase inhibitory activities. The protein kinase activity was performed to evaluate their anticancer activities. All the compounds possess drug‐like characters as they followed Lipinski's rule of five (RO5). Almost all the compounds showed no to fewer toxicities. In addition, other than the compounds, that is, 6a, 6b, 6c, 6m, 6n, 6p, and 6s, the rest of the compounds showed good α‐glucosidase inhibitory potential (IC50 7.17 ± 0.201 to 74.08 ± 0.244 μg/ml) when compared with acarbose standard (IC50 16.59 ± 0.135 μg/ml). All compounds had moderate to good inhibitory potential against the α‐amylase enzyme, with IC50 values ranging from 12.00 ± 0.289 to 76.15 ± 0.477 μg/ml. Eleven analogs (6e, 6f, 6g, 6h, 6j, 6k, 6l, 6n, 6o, 6p, and 6r) showed good to moderate activity. Seven analogs (6a, 6b, 6c, 6d, 6i, 6m, and 6s) showed no α‐amylase inhibitory activity. The protein kinase inhibition potential was determined for the first time, and the compounds 6d, 6e, 6f, 6h, 6k, 6p, and 6r depicted activity with the zone of inhibition in the range of 9 ± 1.3 to 19 ± 1.5 mm. The ligands and active site binding interactions of α‐glucosidase, α‐amylase, and protein kinase enzymes were also studied using molecular modeling. [ABSTRACT FROM AUTHOR]

The validation of underexplored traditional plant remedies represents a reservoir of novel leads for drug discovery. In line with this, in vitro total phenolics and flavonoids content, multimode antioxidants, antimicrobial, cytotoxicity, and protein kinase inhibition assays were conducted on C. ambrosioides seed extracts in addition to RP-HPLC. Methanol extract exhibited highest total phenolics (64.6 ± 0.6 μ g gallic acid equivalent/mg) and flavonoids (50.9 ± 0.5 μ g quercetin equivalent/mg) content. RP-HPLC quantified rutin (1.98 μg/mg) in methanol extract whereas quercetin (0.322 μg/mg) and kaempferol (2.86 μg/mg) in methanol-distilled water extract. Methanol extract exhibited highest ascorbic acid equivalent (AAE) free radical (DPPH) scavenging (IC50 of 110.7 ± 5 μ g / ml), total antioxidant capacity (110.6 ± 2.2 μ g AAE/mg), and total reducing power (94.30 ± 0.46 μ g AAE/mg). Highest antibacterial activity against K. pneumonia (14 ± 1.61 mm ZOI) and antifungal activity against F. solani (17 ± 1.38 mm ZOI) were shown by n-hexane and chloroform extracts, respectively. Ethyl acetate extract exhibited highest brine shrimps cytotoxicity (LC50 of 125 μg/ml). A noteworthy protein kinase inhibitory potential was shown by ethanol extract with a 20 ± 1.27 mm bald zone. Therapeutic potential of medicinal plants can be completely explored by using multiple solvent system. This study makes C. ambrosioides, a resourceful prospect for the bioactivity-guided isolation of lead compounds. [ABSTRACT FROM AUTHOR]

Ipomoea carnea Jacq. is an important folklore medicinal plant, assessed for its underexplored biological potential. Antioxidant, cytotoxic, antiproliferative and polyphenolic profile of whole plant was evaluated using various techniques. Maximum extract recovery (29% w/w), phenolic [13.54 ± 0.27 μg GAE/mg dry weight (DW)] and flavonoid (2.11 ± 0.10 μg QE /mg DW) content were recorded in methanol-distilled water (1:1) flower extract. HPLC-DAD analysis quantified substantial amount of six different polyphenols ranging from 0.081 to 37.95 μg/mg extract. Maximum total antioxidant and reducing potential were documented in methanol-distilled water and acetone-distilled water flower extracts (42.62 ± 0.47 and 24.38 ± 0.39 μg AAE/mg DW) respectively. Ethanol-chloroform root extract manifested highest free radical scavenging (IC50 of 61.22 μg/mL) while 94.64% of the extracts showed cytotoxicity against brine shrimps. Ethanol leaf extract exhibited remarkable activity against THP-1 cell line (IC50 = 8 ± 0.05 μg/mL) and protein kinases (31 mm phenotype bald zone). [ABSTRACT FROM AUTHOR]

The current study was intended to explore the phytochemical profiling and therapeutic activities of Putranjiva roxburghii Wall. Crude extracts of different plant parts were subjected to the determination of antioxidant, antimicrobial, antidiabetic, cytotoxic, and protein kinase inhibitory potential by using solvents of varying polarity ranges. Maximum phenolic content was notified in distilled water extracts of the stem (DW-S) and leaf (DW-L) while the highest flavonoid content was obtained in ethyl acetate leaf (EA-L) extract. HPLC-DAD analysis confirmed the presence of various polyphenols, quantified in the range of 0.02 ± 0.36 to 2.05 ± 0.18 μg/mg extract. Maximum DPPH scavenging activity was expressed by methanolic extract of the stem (MeOH-S). The highest antioxidant capacity and reducing power was shown by MeOH-S and leaf methanolic extract (MeOH-L), respectively. Proficient antibacterial activity was shown by EA-L extract against Bacillus subtilis and Escherichia coli. Remarkable α-amylase and α-glucosidase inhibition potential was expressed by ethyl acetate fruit (EA-F) and n-Hexane leaf (nH-L) extracts, respectively. In case of brine shrimp lethality assay, 41.67% of the extracts (LC50 < 50 µg/mL) were considered as extremely cytotoxic. The test extracts also showed mild antifungal and protein kinase inhibition activities. The present study explores the therapeutic potential of P. roxburghii and calls for subsequent studies to isolate new bioactive leads through bioactivity-guided isolation. [ABSTRACT FROM AUTHOR]

Solubility of phytoconstituents depends on the polarity of the extraction medium used, which might result in the different pharmacological responses of extracts. In line with this, ethnomedicinally important food plant (i.e., Caralluma tuberculata extracts) have been made in fourteen distinct solvent systems that were then analyzed phytochemically via total phenolic amount estimation, total flavonoid amount estimation, and HPLC detection and quantification of the selected polyphenols. Test extracts were then subjected to a battery of in vitro assays i.e., antioxidants (DDPH scavenging, antioxidant capacity, and reducing power estimation), antimicrobial (antibacterial, antifungal, and antileishmanial), cytotoxic (brine shrimps, THP-1 human leukemia cell lines and normal lymphocytes), and protein kinase inhibition assays. Maximum phenolic and flavonoid contents were computed in distilled water–acetone and acetone extracts (i.e., 16 ± 1 μg/mg extract and 8 ± 0.4/mg extract, respectively). HPLC-DAD quantified rutin (0.58 µg/mg extract) and gallic acid (0.4 µg/mg extract) in methanol–ethyl acetate and methanol extracts, respectively. Water–acetone extract exhibited the highest DPPH scavenging of 36 ± 1%. Total reducing potential of 76.0 ± 1 μg/mg extract was shown by ethanol chloroform while maximum total antioxidant capacity was depicted by the acetone extract (92.21 ± 0.70 μg/mg extract). Maximal antifungal effect against Mucor sp., antileishmanial, brine shrimp cytotoxicity, THP-1 cell line cytotoxicity, and protein kinase inhibitory activities were shown by ethyl acetate-methanol (MIC: 50 µg/disc), n-hexane (IC50: 120.8 ± 3.7 µg/mL), ethyl acetate (LD50: 29.94 ± 1.6 µg/mL), distilled water–acetone (IC50: 118 ± 3.4 µg/mL) and methanol–chloroform (ZOI: 19 ± 1 mm) extracts, respectively. Our findings show the dependency of phytochemicals and bioactivities on the polarity of the extraction solvent and our preliminary screening suggests the C. tuberculata extract formulations to be tested and used in different ailments, however, detailed studies remain necessary for corroboration with our results. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is an aggressive disease and, despite advances, its treatment remains challenging. Therefore, it remains important to identify new agents for the management of this disease. Withanolides, a group of steroidal lactones found in Solanaceae plants are of potential interest due to their reported anticancer activities in different settings. In this study we investigated the anti-proliferative effects and mode of action of Solanaceae-derived withanolides in AML cell models; these metabolites include withametelin (WTH) and Coagulansin A (CoA) isolated from Datura innoxia and Withania coagluanse, respectively. Both withanolides inhibited the proliferation of AML cells and induced cell death, with WTH being more potent than CoA in the AML models tested. Quantitative label-free proteomics and phosphoproteomics were employed to define the mechanism of action of the studied withanolides. We identified and quantified 5269 proteins and 17,482 phosphosites in cells treated with WTH, CoA or vehicle control. Withanolides modulated the expression of proteins involved in regulating key cellular processes including cell cycle, metabolism, signaling, protein degradation and gene expression. Enrichment analysis of the phosphoproteomics data against kinase substrates, kinase-kinase relationships and canonical pathways showed that the withanolides decreased the activity of kinases such as phosphoinositide 3-kinase (PI3K), protein kinase B (PKB; also known as RAC-alpha serine/threonine-protein kinase or AKT), mammalian target of rapamycin (mTOR), extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) and the serine/threonine-protein kinase A-Raf (ARAF), while increasing the activation of DNA repair kinases. These results indicate that withanolide metabolites have pleiotropic effects in the modulation of oncogenic pro-survival and pro-apoptotic signaling pathways that regulate the induction of apoptosis. Withanolide mediated apoptosis was confirmed by immunoblotting showing increased expression of cleaved PARP and Caspases 3, 8 and 9 as a result of treatment. Overall, our results suggest that WTH and CoA have therapeutic potential against AML with WTH exhibiting more potent effects and should be explored further. [ABSTRACT FROM AUTHOR]

• Pd(II)-NHC complexes used as catalysts in direct C H arylation reaction of caffeine. • The C8-(hetero)aryl xanthines were obtained in good to excellent yields. • Different C8-(hetero)aryl xanthines which are important to biological applications were synthesised for the first time. • Molecular docking, antioxidant, antifungal, antibacterial and enzyme inhibitory evaluations of 8-(hetero)aryl xanthines were examined. A series of 8-(hetero)aryl caffeine was synthesized by the C H bond activation reaction using Pd-NHCs complexes as a catalyst. 8-(hetero)aryl caffeine derivatives were screened for their antioxidant, antimicrobial, and enzyme inhibitory activities and in-silico studies. The 4a, 4b, 4e, 4f, 4 g, 4i, and 4n showed significant total antioxidant capacity (TAC) of 64.03, 50.87, 70.02, 98.14, 71.81, 45.48, and 44.28 µg AAE/mg, respectively. The 4a, 4b, 4d, 4e, 6 h, 4i, 4j, 4k, and 4l were found active against Staphylococcus aureus at a minimum inhibitory concentration of 25, 12.5, 12.5, 12.5, 12.5, 6.25, 6.25, 6.25, and 6.25 µg/ml, respectively. Some derivatives displayed activity against Escherichia coli, Bacillus subtilus, Klebsiella pneumonae, and Pseudomonas aeruginosa. A good activity was exhibited against Alternaria solani among five fungal strains. All the compounds (4a–4n) showed excellent protein kinase inhibitory activity except 4e, 4 g, and 4n. Additionally, 8-(hetero)aryl caffeine derivatives showed α-amylase inhibition potential (IC50 = 1.49 ± 0.317 to 7.44 ± 0.156 μg/ml) compared to standard acarbose (IC50 = 4.34 ± 0.333 μg/ml). The 4b, 4d, 4j, 4 m, and 4n compounds displayed good α-glucosidase inhibitory potential. Molecular modeling was done for protein kinase, α-amylase, and α-glucosidase. The results of these activities proved the caffeine derivatives to be bioactive. [Display omitted] [ABSTRACT FROM AUTHOR]

• Synthesis of arylidenehydrazinylthiazole carbohydrazides with varying electonic properties of the aryidene group • Structures were analyzed through different spectroscopic techniques. • The experimental results show good agreement with theoretical results. • NLO and electronic properties were also studied. Hydrazide scaffold is very significant in medicinal and synthetic chemistry. Hydrazides lead to heterocyclic pharmacophores exhibiting substantial physicochemical properties. Synthesis of 2-(2-(arylidene)hydrazinyl)thiazole-4-carbohydrazides (BHTC1-BHTC6) (48–69%), was accomplished through multistep sequence, incorporating variable electronic properties in the arylidene moiety. The structures of the accomplished synthetic design were established via FT-IR, HRMS, 1H and 13CNMR. The α -Amylase study of all new compounds showed percentage inhibition values within the range of 17.78±0.023 to 31.00±0.19 at 50 µg/mL as compared to acarbose (85.56±0.56, at 50 µg/mL). However, the synthesized compounds also exhibited moderate to good protein kinase inhibition as well. The computational analyses were also accomplished for BHTC1-BHTC6 at M06 functional with a 6–31G(d,p) basis set. To elucidate the stability and ICT of the compounds, NBO and FMO analyses were conducted. The synthesized compound BHTC6 displayed the lowest bandgap value, i.e., 4.355 eV among BHTC1-BHTC5. The global reactivity parameters were correlated with their bandgap data and BHTC6 was concluded to express a high value of softness and a low hardness value among entitled compounds. Moreover, UV–Vis analysis indicates that BHTC6 is the most bathochromically shifted among all designed compounds, possessing λ max of 381.534 nm. The aforementioned results reveal that these compounds may prove significant in developing better enzyme inhibitors or antimicrobial agents. [Display omitted] [ABSTRACT FROM AUTHOR]