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We report herein the synthesis, docking studies and biological evaluation of a series of new 4-chloro-2-((5-aryl-1,3,4-oxadiazol-2-yl)amino)phenol analogues (6a-h). The new compounds were designed based on the oxadiazole-linked aryl core of tubulin inhibitors of IMC-038525 and IMC-094332, prepared in five steps and further characterized via spectral analyses. The anticancer activity of the compounds was assessed against several cancer cell lines belonging to nine different panels as per National Cancer Institute (NCI US) protocol. 4-Chloro-2-((5-(3,4,5-trimethoxyphenyl)-1,3,4-oxadiazol-2-yl)amino)phenol (6h) demonstrated significant anticancer activity against SNB-19 (PGI = 65.12), NCI-H460 (PGI = 55.61), and SNB-75 (PGI = 54.68) at 10 µM. The compounds were subjected to molecular docking studies against the active site of the tubulin–combretastatin A4 complex (PDB ID: 5LYJ); they displayed efficient binding and ligand 4h (with docking score = −8.030 kcal/mol) lay within the hydrophobic cavity surrounded by important residues Leu252, Ala250, Leu248, Leu242, Cys241, Val238, Ile318, Ala317, and Ala316. Furthermore, the antibacterial activity of some of the compounds was found to be promising. 4-Chloro-2-((5-(4-nitrophenyl)-1,3,4-oxadiazol-2-yl)amino)phenol (6c) displayed the most promising antibacterial activity against both Gram-negative as well as Gram-positive bacteria with MICs of 8 µg/mL and a zone of inhibition ranging from 17.0 ± 0.40 to 17.0 ± 0.15 mm at 200 µg/mL; however, the standard drug ciprofloxacin exhibited antibacterial activity with MIC values of 4 µg/mL. [ABSTRACT FROM AUTHOR]

We reported herein a green and efficient catalyst-free synthesis of 4'-(substituted phenyl)spiro[indoline-3,3'-[1,2,4]triazolidine]-2,5'-diones (3a–g) in excellent yields. A one-pot multi-component synthesis was achieved using a glycerol-water (4:1) green solvent system. The current synthetic procedure has the advantage of being environmentally friendly, catalyst free, and having a simple workup with high yields. The structure of the title compounds (3a–g) was confirmed by infrared (IR), nuclear magnetic resonance (NMR) and mass spectral data, followed by their biological evaluation. Using the standard protocol, all of the compounds were tested for antibacterial, antifungal, and antitubercular activities. 4'-(4-Chlorophenyl)spiro[indoline-3,3'-[1,2,4]triazolidine]-2,5'-dione (3b) was found to be the most potent compound in the series, with MIC values ranging from 12.71 to 50.84 M, but it was found to be inactive against Mycobacterium tuberculosis H37Ra and M. bovis. 4'-(4-Methoxyphenyl)spiro[indoline-3,3'-[1,2,4]triazolidine]-2,5'-dione (3e) displayed significant antifungal activity with MIC values of 12.89 and 25.78 µM. The SwissADME prediction studies of revealed that the compounds (3a–g) followed the Lipinski rule of 5 and have good absorption from gastrointestinal tract. The title compounds were also investigated using molecular docking against bacterial DNA gyrase (PDB ID: 1KZN). [ABSTRACT FROM AUTHOR]

The current research focuses on the utilization of cobalt ferrite and Al-doped cobalt ferrite as catalysts for the synthesis of 12-aryl/heteroaryl-8,9,10,12-tetrahydrobenzo[a]xanthene-11-ones derivatives in semi-aqueous conditions. Doping some aluminum metal into CoFe2O4 improved its catalytic potential, which was then utilized in chemical synthesis. The produced catalyst was recycled in numerous reactions to test its stability. Characterization of the catalysts was done using FT-IR, XRD, BET, and SEM techniques. The grade of the catalysts was also determined by the yield of xanthene derivatives. The effect of pure cobalt ferrite and varied molar ratios of aluminum cobalt ferrite on the yield and reaction time of xanthene derivatives has been thoroughly explored. Xanthene derivatives having aryl moiety showed better results in terms of reaction times and yield as compared to heteroaryl. Cost-effective, recyclable catalysts producing excellent yield in short reaction time, with easy work method are some salient features of current research. [ABSTRACT FROM AUTHOR]

The chemical industry is one of the main fossil fuel consumers, so its reliance on sustainable and renewable resources such as wind and solar energy should be increased to protect the environment. Accordingly, solar-driven thermocatalytic synthesis of octahydroquinazolinone using polyvinylchloride (PVC)-supported aluminum oxide (Al2O3) as a catalyst under natural sunlight is proposed in this work. The Al2O3/PVC catalysts were characterized by FT-IR, SEM, BET, XRD, and XPS techniques. The obtained results indicate that the yield and reaction time can be modified by adjusting the molar ratio of the catalyst. To investigate the stability of the catalyst, the spent catalyst was reused in several reactions. The results indicated that, when a 50% Al2O3 catalyst is employed in an absolute solar heat, it performs exceptionally well in terms of yield (98%) and reaction time (35 min). Furthermore, the reaction times and yield of octahydroquinazolinone derivatives with an aryl moiety were superior to those of heteroaryl. All the synthesized compounds were well characterized by FT-IR, 1H-NMR, and 13C-NMR. The current work introduces a new strategy to use solar heat for energy-efficient chemical reactions using a cost-effective, recyclable environmentally friendly PVC/Al2O3 catalyst that produces a high yield. [ABSTRACT FROM AUTHOR]

Metal nanoparticles use a biocompatible, environmentally sustainable approach to be used as therapeutic nanomedicine. This study describes the use of rosaceous fruit peel waste extract (plum, kiwi, peach) as a tool for the synthesis of silicon nanoparticles. Visual color shift was used to identify biosynthesized SiO2NPs at first. Some characterization techniques, such as X-ray diffraction (XRD), Fourier transform infrared (FT-IR) and SEM analysis, verified the existence of these metal nanoparticles. The presence of various functional groups from the extract secondary metabolites for nanoparticle synthesis is suggested by FT-IR spectroscopy. The existence of SiO2 nanoparticles, whether crystalline or amorphous, is hypothesized using XRD. The formation of SiO2 nanoparticles was confirmed by UV–Vis spectroscopy. The zeta potential shows the nanoparticles stability. Different fruits peels produced different shapes and sizes of SiO2NPs. Plum peels extract produced the smallest SiO2NPs, followed by kiwi and peach as determined by SEM analysis. Antibacterial and antioxidant activities were also tested on all of the synthesized SiO2NPs. Regardless of size; these nanoparticles have stronger antibacterial activity against gram-negative bacteria. All SiO2NPs' antioxidant activity was measured in a size and dose-dependent manner. To summarize, the current environmentally friendly method for the synthesis of SiO2NPs nanoparticles is a simple and economical process with good antibacterial and antioxidant properties. The biosynthesis characterization and biological activity evaluation of silicon dioxide (SiO2) nanoparticles were investigated by utilizing wastes of some fruit peels belonging to Rosaceae family (fruit peels of plum, kiwi and peach). [ABSTRACT FROM AUTHOR]

With 19.3 million new cases and almost 10 million deaths in 2020, cancer has become a leading cause of death today. Curcumin and its analogues were found to have promising anticancer activity. Inspired by curcumin's promising anticancer activity, we prepared three semi-synthetic analogues by chemically modifying the diketone function of curcumin to its pyrazole counterpart. The curcumin analogues (3a–c) were synthesized by two different methods, followed by their DFT analyses to study the HOMO/LUMO configuration to access the stability of compounds (∆E = 3.55 to 3.35 eV). The curcumin analogues (3a–c) were tested for antiproliferative activity against a total of five dozen cancer cell lines in a single (10 µM) and five dose (0.001 to 100 µM) assays. 3,5-Bis(4-hydroxy-3-methoxystyryl)-1H-pyrazole-1-yl-(phenoxy)ethanone (3b) and 3,5-bis(4-hydroxy-3-methoxystyryl)-1H-pyrazole-1-yl-(2,4-dichlorophenoxy)ethanone (3c) demonstrated the most promising antiproliferative activity against the cancer cell lines with growth inhibitions of 92.41% and 87.28%, respectively, in a high single dose of 10 µM and exhibited good antiproliferative activity (%GIs > 68%) against 54 out of 56 cancer cell lines and 54 out of 60 cell lines, respectively. The compound 3b and 3c demonstrated the most potent antiproliferative activity in a 5-dose assay with GI50 values ranging between 0.281 and 5.59 µM and 0.39 and 0.196 and 3.07 µM, respectively. The compound 3b demonstrated moderate selectivity against a leukemia panel with a selectivity ratio of 4.59. The HOMO-LUMO energy-gap (∆E) of the compounds in the order of 3a > 3b > 3c, was found to be in harmony with the anticancer activity in the order of 3c ≥ 3b > 3a. Following that, all of the curcumin analogues were molecular docked against EGFR, one of the most appealing targets for antiproliferative activity. In a molecular docking simulation, the ligand 3b exhibited three different types of interactions: H-bond, π-π-stacking and π-cationic. The ligand 3b displayed three H-bonds with the residues Met793 (with methoxy group), Lys875 (with phenolic group) and Asp855 (with methoxy group). The π-π-stacking interaction was observed between the phenyl (of phenoxy) and the residue Phe997, while π-cationic interaction was displayed between the phenyl (of curcumin) and the residue Arg841. Similarly, the ligand 3c displayed five H-bonds with the residue Met793 (with methoxy and phenolic groups), Lys845 (methoxy group), Cys797 (phenoxy oxygen), and Asp855 (phenolic group), as well as a halogen bond with residue Cys797 (chloro group). Furthermore, all the compound 3a–c demonstrated significant binding affinity (−6.003 to −7.957 kcal/mol) against the active site of EGFR. The curcumin analogues described in the current work might offer beneficial therapeutic intervention for the treatment and prevention of cancer. Future anticancer drug discovery programs can be expedited by further modifying these analogues to create new compounds with powerful anticancer potentials. [ABSTRACT FROM AUTHOR]

Natural products (NPs) continue to provide a structural template for the design of novel therapeutic agents and expedite the drug discovery process. The majority of FDA-approved pharmaceuticals used in medical practice can be traced back to natural sources, and NPs play a significant role in drug development. Curcumin, one of the most well-studied chemicals among the NPs, is currently the subject of intense investigation for its biological effects, including the prevention and treatment of cancer. Cancer has overtaken all other causes of death in the world today, with 19.3 million new cases and nearly 10 million deaths predicted in 2020. In the present investigation, we reported the synthesis of three semi-synthetic analogues of curcumin-bearing pyrimidinone moiety by the chemical modification of the diketone function of curcumin followed by their characterization by analytical techniques including infrared (IR), nuclear magnetic resonance (NMR), and mass spectral data. According to the National Cancer Institute (NCI US) methodology, the curcumin analogues (C1-C3) were tested for their anticancer efficacy against 59 cancer cell lines in a single dose assay. 1-(2,6-Dichlorophenyl)-4,6-bis((E)-4-hydroxy-3-methoxystyryl)pyrimidin-2(1H)-one (C2) demonstrated the most promising anticancer activity with mean percent growth inhibition (%GIs) of 68.22 in single dose assay at 10 µM. The compound exhibited >68 %GIs against 31 out of 59 cancer cell lines and was found to be highly active against all leukemia and breast cancer cell lines. The compound C2 showed a lethal effect on HT29 (colon cancer) with %GI of 130.44, while 99.44 %GI was observed against RPMI-8226 (Leukemia). The compound C2 displayed better anticancer activity against the panels of CNS, melanoma, ovarian, prostate, and breast cancer cell lines than curcumin and other anti-EGFR agents gefitinib and imatinib in single dose assay. The compound C2 also demonstrated potent anticancer activity in a 5-dose assay (0.001 to 100 µM) with GI50 values ranging from 1.31 to 4.68 µM; however, it was found to be non-selective with SR values ranging from 0.73 to 1.35. The GI50 values of compound C2 were found to be better than that of the curcumin against all nine panels of cancer cell lines. All of the curcumin analogues were subsequently investigated for molecular docking simulation against EGFR, one of the most attractive targets for antiproliferative action. In molecular docking studies, all the ligands were found to accommodate the active site of EGFR and the binding affinity of ligand C2 was found to be −5.086 kcal/mol. The ligand C2 exhibited three different types of interactions: H-bond (Thr790 and Thr854), π-cationic (Arg841), and aromatic H-bond (Asn842). The curcumin analogues reported in the current investigation may provide valuable therapeutic intervention for the prevention and treatment of cancer and accelerate anticancer drug discovery programs in the future. [ABSTRACT FROM AUTHOR]

Zn:Cr mixed oxide catalyst was examined as an effective and recyclable catalyst for the synthesis selected pyrimidine derivatives in high yield. The catalyst was characterized by FT-IR, XRD, BET, SEM, EDX and Zeta potential analysis. Substituted 4-aryl-6-(3-coumarinyl) pyrimidine-2(1H)-ones were prepared in high yield and purity via the cyclocondensation of urea and 3-acetylcoumarin with substituted aldehydes in the presence of a catalytic amount of Zn:Cr mixed oxide catalyst as Lewis acid at ambient temperature. The effect of the molar ratio of the catalyst was also studied, and as a result, Zn:Cr (10:1) showed better catalytic performance than Zn:Cr (1:1) at identical reaction conditions. Furthermore, catalyst stability was intact as confirmed by the catalyst recyclability experiment. [ABSTRACT FROM AUTHOR]

An efficient, recyclable silica supported tungstophosphoric acid (HPW/SiO2) catalyst was prepared by simple stirring method. The catalyst was characterized using FT-IR, X-ray diffraction (XRD), Brunauer–Emmett–Teller (BET), and scanning electron microscopy (SEM) techniques. The catalyst was explored in semi aqueous condition toward synthesis of 1,8-dioxoacridine carboxylic acid derivatives. It was recycled up to four runs and a very marginal loss was detected. The targeted compounds were synthesized in a very short time period and simple work procedure with excellent yield. [ABSTRACT FROM AUTHOR]

Ever since, traditional plants and their products were consumed by human beings in diverse health matters to heal variety of infections. At the moment, in all over globe, the scientific attention and focuses are escalating with regard to phytomedicine. This study explores the value of secondary metabolites of Emblica officinalis leaves extract (EOLE) identified through GCMS/MS profiling in different solvents against microbial strains. In-vitro antimicrobial activity was established by means of an agar well diffusion scheme at various loaded concentrations (25 µg/mL-1000 µg/mL). GC-MS/MS profiling confirmed the presence of major accredited compounds characterized as PDMTFM (Rt-9.891 min and peak area-1.77%), P2,6-BDME (Rt-8.588 min, peak area - 100%), P2,5-BDME (Rt - 8.567 min, peak area - 36.78%) and BFTHTM (Rt-9.055 min, peak area - 7.87%) in tag plant. Gram positive bacteria; Bacillus pumilis, Bacillus cereus, Staphylococcus pyogenous, Bacillus polymyxa and Gram negative bacteria; Vibrio cholera, Providencia alcalifaciens, while fungal species; Neurospora crassa, Trichoderma viridae, Aspergillus brasileinsis and Cladosporium oxysporum were used during this study. Aqueous extract made known excellent antimicrobial activity than other selected extract. Inhibitory values of aqueous and methanolic extract were measured with reference to ciprofloxacin and amphotericin. Preliminary results of this study implied that EOLE could be considered as strong antimicrobial agent to treat human infectious diseases. [ABSTRACT FROM AUTHOR]

Biosynthetic procedure is the best alternative to the preparation of nonmaterials as the challenges faced by the scientist from the last few decades. Present research reports cost-effective, inexpensive eco-friendly synthesis of titanium dioxide nanoparticles using a methanolic extract of fruits peel agro-waste. X-ray diffraction spectrum of identified TiO2NPs found noncrystalline in nature. Fourier transform infrared showed O–H, C = O, C–O, and C–H functional groups present in the fruit peel involved in the biosynthesis of TiO2NPs. The prominent peak at 1708, 1720 and 1700 cm−1 observed in the spectrum attributed to O–Ti–O stretching in Plum, Kiwi and Peach mediated TiO2NPs. The SEM images of all three TiO2NPs revealed cylindrical in shape. The size of TiO2NPs synthesized from Plum, Kiwi and Peach were found to be 47.1 and 63.2, 54.1 and 85.1 and 200 nm, respectively. All the TiO2NPs exhibited size- and dose-dependent antibacterial and antioxidant activities. [ABSTRACT FROM AUTHOR]

A Palladium-doped silica-supported heteropoly acid (HPW) (1%Pd-HPW/SiO2) bi-functional catalyst was produced using ultrasonic and conventional procedures. Both forms of catalyst were characterized with distinct analytical approaches in order to access the advantages of each one. The presence of the required functional groups in the catalyst was confirmed using FT-IR. The crystallinity of ultrasonically generated 1%Pd-HPW/SiO2 was confirmed with XRD. The existence of necessary elements in the catalyst was also suggested by XPS and EDX data. BET was used to calculate the surface area of the ultrasonically synthesized catalyst (395 m2 g−1), and it was found to be greater than that of the non-ultrasonic synthesized catalyst (382 m2 g−1). The N2 adsorption-desorption isotherm indicated mesoporous structures. The SEM morphology at a similar magnification exhibited quite different shapes. In comparison to traditional methods, ultrasonic approaches produce higher yields in less time and use less energy. Furthermore, the effect of the preparation method of the 1%Pd-HPW/SiO2 catalyst was extensively studied with respect to the synthesis of octahydroquinazolinones. Excellent product yields, a fast reaction time, and simple work-up methods are some peculiarities associated with the ultrasonically synthesized catalyst. The recycling study was also investigated and found suitable for up to four reaction cycles. [ABSTRACT FROM AUTHOR]

Cancer is the world's second leading cause of death, accounting for nearly 10 million deaths and 19.3 million new cases in 2020. Curcumin analogs are gaining popularity as anticancer agents currently. We reported herein the isolation, molecular engineering, molecular docking, antiproliferative, and anti-epidermal growth factor receptor (anti-EGFR) activities of curcumin analogs. Three curcumin analogs were prepared and docked against the epidermal growth factor receptor (EGFR), revealing efficient binding. Antiproliferative activity against 60 NCI cancer cell lines was assessed using National Cancer Institute (NCI US) protocols. The compound 3b,c demonstrated promising antiproliferative activity in single dose (at 10 µM) as well as five dose (0.01, 0.10, 1.00, 10, and 100 µM). Compound 3c inhibited leukemia cancer panel better than other cancer panels with growth inhibition of 50% (GI50) values ranging from 1.48 to 2.73 µM, and the most promising inhibition with GI50 of 1.25 µM was observed against leukemia cell line SR, while the least inhibition was found against non-small lung cancer cell line NCI-H226 with GI50 value of 7.29 µM. Compounds 3b,c demonstrated superior antiproliferative activity than curcumin and gefitinib. In molecular docking, compound 3c had the most significant interaction with four H-bonds and three π–π stacking, and compound 3c was found to moderately inhibit EGFR. The curcumin analogs discovered in this study have the potential to accelerate the anticancer drug discovery program. [ABSTRACT FROM AUTHOR]

Protein kinase inhibitors (PKIs) are important therapeutic agents. As of 31 May 2021, the United States Food and Drug Administration (USFDA) has approved 70 PKIs. Most of the PKIs are employed to treat cancer and inflammatory diseases. Imatinib was the first PKI approved by USFDA in 2001. This review summarizes the compound patents and the essential polymorph patents of the PKIs approved by the USFDA from 2001 to 31 May 2021. The dates on the generic drug availability of the PKIs in the USA market have also been forecasted. It is expected that 19 and 48 PKIs will be genericized by 2025 and 2030, respectively, due to their compound patent expiry. This may reduce the financial toxicity associated with the existing PKIs. There are nearly 535 reported PKs. However, the USFDA approved PKIs target only about 10–15% of the total said PKs. As a result, there are still a large number of unexplored PKs. As the field advances during the next 20 years, one can anticipate that PKIs with many scaffolds, chemotypes, and pharmacophores will be developed. [ABSTRACT FROM AUTHOR]

The present research was performed to assess the effect of 24-epibrassinolide (EBR) on salt-stressed soybean plants. Salt stress suppressed growth, biomass yield, gas exchange parameters, pigment content, and chlorophyll fluorescence, but all these parameters were up-regulated by EBR supply. Moreover, salt stress increased hydrogen peroxide, malondialdehyde, and electrolyte leakage. EBR supplementation reduced the accumulation of oxidative stress biomarkers. The activities of superoxide dismutase and catalase, and the accumulation of proline, glycinebetaine, total phenols, and total flavonoids increased with NaCl stress, but these attributes further increased with EBR supplementation. The activities of enzymes and the levels of non-enzymatic antioxidants involved in the Asc-Glu cycle also increased with NaCl stress, and further enhancement in these attributes was recorded by EBR supplementation. Salinity elevated the methylglyoxal content, but it was decreased by the EBR supplementation accompanying with up-regulation of the glyoxalase cycle (GlyI and GlyII). Salinity enhanced the Na+ uptake in root and shoot coupled with a decrease in uptake of Ca2+, K+, and P. However, EBR supplementation declined Na+ accumulation and promoted the uptake of the aforementioned nutrients. Overall, EBR supplementation regulated the salt tolerance mechanism in soybean plants by modulating osmolytes, activities of key enzymes, and the levels of non-enzymatic antioxidants. [ABSTRACT FROM AUTHOR]