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In this study, a new series of 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N’-(2-(substituted)acetyl) benzohydrazides (5a–n) were prepared and new heterocycles underwent thorough characterization and evaluation for antibacterial activity; some of them underwent further testing for in vitro inhibition of enoyl ACP reductase and DHFR enzymes. The majority of the synthesized molecules exhibited appreciable action against DHFR and enoyl ACP reductase enzymes. Some of the synthesized compounds also showed strong antibacterial and antitubercular properties. In order to determine the potential mode of action of the synthesized compounds, a molecular docking investigation was conducted. The results revealed binding interactions with both the dihydrofolate reductase and enoyl ACP reductase active sites. These molecules represent excellent future therapeutic possibilities with potential uses in the biological and medical sciences due to the compounds’ pronounced docking properties and biological activity.

Diabetes mellitus (DM) is counted among one of the leading challenges in the recent era, and it is a life-threatening disorder. Compound 4-hydroxy 3-methoxy phenylacetone (compound 1) was previously isolated from Polygonumaviculare. This compound was reacted with N-benzylmaleimide to synthesize the targeted compound 3. The purpose of this research is to exhibit our developed compound 3’s ability to concurrently inhibit many targets that are responsible for hyperglycemia. Compound 3 was capable of inhibiting α-amylase, α-glucosidase, and protein tyrosine phosphatase 1 B. Even so, outstanding in vitro inhibition was shown by the compound against dipeptidyl peptidase-4 (DPP-4) with an IC50 value of 0.07 µM. Additionally, by using DPPH in the antioxidant activity, it exhibited good antioxidant potential. Similarly, in the in vivo activity, the experimental mice proved to be safe by treatment with compound 3. After 21 days of examination, the compound 3 activity pattern was found to be effective in experimental mice. Compound 3 decreased the excess peak of total triglycerides, total cholesterol, AST, ALT, ALP, LDL, BUN, and creatinine in the STZ-induced diabetic mice. Likewise, the histopathology of the kidneys, liver, and pancreas of the treated animals was also evaluated. Overall, the succinimde moiety, such as compound 3, can affect several targets simultaneously, and, finally, we were successful in synthesizing a multi-targeted preclinical therapy.

Cancer is characterized by the abnormal development of cells that divide in an uncontrolled manner and further take over the body and destroy the normal cells of the body. Although several therapies are practiced, the demand and need for new therapeutic agents are ever-increasing because of issues with the safety, efficacy and efficiency of old drugs. Several plant-based therapeutics are being used for treatment, either as conjugates with existing drugs or as standalone formulations. Withania somnifera (L.) Dunal is a highly studied medicinal plant which is known to possess immunomodulatory activity as well as anticancer properties. The pivotal role of KAT6A in major cellular pathways and its oncogenic nature make it an important target in cancer treatment. Based on the literature and curated datasets, twenty-six compounds from the root of W. somnifera and a standard inhibitor were docked with the target KAT6A using Autodock vina. The compounds and the inhibitor complexes were subjected to molecular dynamics simulation (50 ns) using Desmond to understand the stability and interactions. The top compounds (based on the docking score of less than −8.5 kcal/mol) were evaluated in comparison to the inhibitor. Based on interactions at ARG655, LEU686, GLN760, ARG660, LEU689 and LYS763 amino acids with the inhibitor WM-8014, the compounds from W. somnifera were evaluated. Withanolide D, Withasomniferol C, Withanolide E, 27-Hydroxywithanone, Withanolide G, Withasomniferol B and Sitoindoside IX showed high stability with the residues of interest. The cell viability of human breast cancer MCF-7 cells was evaluated by treating them with W. Somnifera root extract using an MTT assay, which showed inhibitory activity with an IC50 value of 45 µg/mL. The data from the study support the traditional practice of W. somnifera as an anticancer herb.

Oral cancer has a high mortality rate, which is mostly determined by the stage of the disease at the time of admission. Around half of all patients with oral cancer report with advanced illness. Hitherto, chemotherapy is preferred to treat oral cancer, but the emergence of resistance to anti-cancer drugs is likely to occur after a sequence of treatments. Curcumin is renowned for its anticancer potential but its marred water solubility and poor bioavailability limit its use in treating multidrug-resistant cancers. As part of this investigation, we prepared and characterized Curcumin nanomicelles (CUR-NMs) using DSPE-PEG-2000 and evaluated the anticancer properties of cisplatin-resistant cancer cell lines. The prepared CUR-NMs were sphere-shaped and unilamellar in structure, with a size of 32.60 ± 4.2 nm. CUR-NMs exhibited high entrapment efficiency (82.2%), entrapment content (147.96 µg/mL), and a mean zeta potential of −17.5ζ which is considered moderately stable. The cellular uptake and cytotoxicity studies revealed that CUR-NMs had significantly higher cytotoxicity and cellular uptake in cisplatin drug-resistant oral cancer cell lines and parental oral cancer cells compared to plain curcumin (CUR). The DAPI and FACS analysis corroborated a high percentage of apoptotic cells with CUR-NMs (31.14%) compared to neat CUR (19.72%) treatment. Conclusively, CUR-NMs can potentially be used as an alternative carrier system to improve the therapeutic effects of curcumin in the treatment of cisplatin-resistant human oral cancer.

Microbial lipases are the biocatalyst of choice for the present and future because of their characteristics, including their ability to remain active as an enzyme throughout a broad pH, temperature, and substrate range. The goal of the current investigation was to find novel sources of substrates and isolates from soil contaminated by oil for the synthesis of lipase. On tributyrin media, 10 lipolytic bacterial strains that were isolated from oil-contaminated soil were grown. Using the zone of clearance, it was possible to identify the isolates with the highest activity. Following phylogenetic tree analysis, molecular characterization of the 16S rRNA sequence of the bacterial isolates revealed that it was Bacillus halotolerans (VSH 09). The enzyme was purified to near homogeneity. The enzyme activity was found to be optimum at a pH of 7.0 and a temperature of 35 °C. While Ni2+ and Cu2+ had no effect, the presence of Mg2+ and Ca2+ exhibited the highest levels of enzyme activity. At 1%, tributyrin as a substrate exhibited its highest level of activity. The molecular weight, as determined by SDS-PAGE, was found to be 38 kDa. The kinetics of the enzyme were found to be 41.66 and 9.37 mg/mL for Vmax and Km, respectively. The high yield of lipase produced by this method suggests that it holds potential for production on a large scale and could be used for various biotechnological applications.

In this article, we describe the fabrication and characterization of a sensor for acute myocardial infarction that detects myoglobin biomarkers using chromium (Cr)-doped zinc oxide (ZnO) nanoparticles (NPs). Pure and Cr-doped ZnO NPs (13 × 1017, 20 × 1017, and 32 × 1017 atoms/cm3 in the solid phase) were synthesized by a facile low-temperature sol-gel method. Synthesized NPs were examined for structure and morphological analysis using various techniques to confirm the successful formation of ZnO NPs. Zeta potential was measured in LB media at a negative value and increased with doping. XPS spectra confirmed the presence of oxygen deficiency in the synthesized material. To fabricate the sensor, synthesized NPs were screen-printed over a pre-fabricated gold-coated working electrode for electrochemical detection of myoglobin (Mb). Cr-doped ZnO NPs doped with 13 × 1017 Cr atomic/cm3 revealed the highest sensitivity of ~37.97 μA.cm−2nM−1 and limit of detection (LOD) of 0.15 nM for Mb with a response time of ≤10 ms. The interference study was carried out with cytochrome c (Cyt-c) due to its resemblance with Mb and human serum albumin (HSA) abundance in the blood and displayed distinct oxidation potential and current values for Mb. Cr-doped ZnO NP-based Mb biosensors showed 3 times higher sensitivity as compared to pure ZnO NP-based sensors.

Indigofera linifolia is a medicinally important plant, and by virtue of its rich phytochemical composition, this plant is widely used as essential component in traditional medication systems. Due to its wide range of medicinal applications, the extract-loaded chitosan (Ext+Ch), extract-loaded PEG (Ext+PEG), and extract-loaded locust bean gum (Ext+LGB) nanoparticles (NPs) were prepared in the present study. The prepared NPs were then evaluated for their antibacterial, antioxidant, and antidiabetic potentials. Antibacterial activities of the crude extract and the synthesized NPs were performed following standard procedures reported in the literature. The antioxidant capabilities of extract and NPs were evaluated using DPPH free radical scavenging assay. The antidiabetic potential of the samples was evaluated against α-amylase and α-glucosidase. Ext+PEG NPs showed more potent antibacterial activity against the selected strains of bacteria with the highest activity against Escherichia coli. The lowest antibacterial potential was observed for Ext+LGB NPs. The Ext+LGB NPs IC50 value of 39 μg/mL was found to be the most potent inhibitor of DPPH free radicals. Ext+LGB NPs showed a greater extent of inhibition against α-glucosidase and α-amylase with an IC50 of 83 and 78 μg/mL, whereas for the standard acarbose the IC50 values recorded against the mentioned enzymes were 69 and 74 μg/mL, respectively. A high concentration of phenolics and flavonoids in the crude extract was confirmed through TPC and TFC tests, HPLC profiling, and GC–MS analysis. It was considered that the observed antibacterial, antidiabetic, and antioxidant potential might be due the presence of these phenolics and flavonoids detected. The plant could thus be considered as a potential candidate to be used as a remedy of the mentioned health complications. However, further research in this regard is needed to isolate the exact responsible compounds of the observed biological potentials exhibited by the crude extract. Further, toxicity and pharmacological evaluations in animal models are also needed to establish the safety or toxicity profile of the plant.

Therapeutic and/or preventive interventions using phytochemical constituents for ischemic heart disease have gained considerable attention worldwide, mainly due to their antioxidant activity. This study investigated the cardioprotective effect and possible mechanism of juglone, a major constituent of the walnut tree, using an isoproterenol (ISO)-induced myocardial infarction (MI) model in rats. Rats were pretreated for five (5) days with juglone (1, 3 mg/kg, i.p) and atenolol (1 mg/kg, i.p) in separate experiments before inducing myocardial injury by administration of ISO (80 mg/kg, s.c) at an interval of 24 h for 2 consecutive days (4th and 5th day). The cardioprotective effect of juglone was confirmed through a lead II electrocardiograph (ECG), cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological study. The results of our present study suggest that prior administration of juglone (1 and 3 mg/kg) proved to be effective as a cardioprotective therapeutic agent in reducing the extent of myocardial damage (induced by ISO) by fortifying the myocardial cell membrane, preventing elevated T-waves, deep Q-waves in the ECG, heart to body weight ratio, infarction and also by normalizing cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological changes, such as inflammation, edema and necrosis. In conclusion, this study has identified phytochemical constituents, in particular juglone, as a potential cardioprotective agent.

The cold extraction method was used to obtain the aqueous extract of Vitex leucoxylon leaves in a ratio of 1:10. Iron nanoparticles (FeNPs) were synthesized using aqueous leaf extract of V. leucoxylon as a reducing agent. The phytoreducing approach was used to make FeNPs by mixing 1 mL of plant extract with 1 mM of ferric sulfate. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), Ultraviolet–visible spectroscopy (UV-Vis), and energy-dispersive X-ray spectroscopy were used to examine the synthesized FeNPs. The reducing reaction was shown by a change in the color of the solution, and the formation of black color confirms that FeNPs have been formed. The greatest absorption peak (max) was found at 395 nm in UV-Vis spectral analysis. The FTIR spectra of V. leucoxylon aqueous leaf extract showed shifts in some peaks, namely 923.96 cm−1 and 1709.89 cm−1, with functional groups carboxylic acids, unsaturated aldehydes, and ketones, which were lacking in the FTIR spectra of FeNPs and are responsible for FeNPs formation. FeNPs with diameters between 45 and 100 nm were observed in SEM images. The creation of FeNPs was confirmed by EDX, which shows a strong signal in the metallic iron region at 6–8 Kev. XRD revealed a crystalline nature and an average diameter of 136.43 nm. Antioxidant, anti-inflammatory, cytotoxic, and wound healing in vitro tests reported significant activity of the FeNPs. The cumulative findings of the present study indicate that the green synthesis of FeNPs boosts its biological activity and may serve as a possible dermal wound-healing agent and cytotoxic agent against cancer. Future study is needed on the identification of mechanisms involved in the synthesis of FeNPs by V. leucoxylon and its biomedical applications.

The applications of bioactive compounds from medicinal plants as therapeutic drugs are largely increasing. The present study selected the bioactive compounds from Acacia concinna (A. concinna) and Citrus limon (C. limon) to assess their phytochemicals, proteins, and biological activity. The plant material was collected, and extraction performed as per the standard procedure. Qualitative analysis was undertaken, and identification of functional organic groups was performed by FTIR and HPLC. Antibacterial, anticancer, antioxidant, antihyperglycemic, antihyperlipidemic, and inhibition kinetics studies for enzymes were performed to assess the different biological activities. Flavonoids and phenols were present in a significant amount in both the selected plants. A. concinna showed significant antimicrobial activity against Z. mobilis, E. coli, and S. aureus, with minimum inhibition zones (MIZ) of 24, 22, and 20 mm, respectively. C. limon strongly inhibited all the tested pathogenic bacteria with maximum and minimum MIZ of 32 and 17 mm. A. concinna silver nanoparticles also exhibited potent antimicrobial activity. Both extracts showed substantial antioxidant, antihyperlipidemic, antidiabetic, anticancer (MCF-7), and anti-urease (antiulcer) properties. To conclude, these plants can be used to treat hyperlipidemia, diabetes, cancer, and gastrointestinal ulcers. They can also serve as antimicrobial and antioxidant agents. Thus, the studied plants must be exploited cost-effectively to generate therapeutic drugs for various diseases.

Over the past few decades, the development of broad-spectrum anticancer agents with anti-angiogenic activity has witnessed considerable progress. In this study, a new series of pyrazolo[3,4-d]pyrimidines based on a phenylfuroxan scaffold were designed, synthesized, and evaluated, in terms of their anticancer activities. NCI-60 cell one-dose screening revealed that compounds 12a–c and 14a had the best MGI%, among the tested compounds. The target fluorinated compound 12b, as the most active one, showed better anticancer activity compared to the reference drug sorafenib, with IC50 values of 11.5, 11.6, and 13 µM against the HepG-2, A2780CP, and MDA-MB-231 cell lines, respectively. Furthermore, compound 12b (IC50 = 0.092 µM) had VEGFR-2-inhibitory activity comparable to that of the standard inhibitor sorafenib (IC50 = 0.049 µM). Furthermore, the ability of compound 12b in modulating MAPK signaling pathways was investigated. It was found to decrease the level of total ERK and its phosphorylated form, as well as leading to the down-regulation of metalloproteinase MMP-9 and the over-expression of p21 and p27, thus leading to subG1 cell-cycle arrest and, thus, the induction of apoptosis. Additionally, compound 12b decreased the rate of wound healing in the absence of serum, in comparison to DMSO-treated cells, providing a significant impact on metastasis inhibition. The quantitative RT-PCR results for E-cadherin and N-cadherin showed lower expression of the neuronal N-cadherin and increased expression of epithelial E-cadherin, indicating the ability of 12b to suppress metastasis. Furthermore, 12b-treated HepG2 cells expressed a low level of anti-apoptotic BCL-2 and over-expressed proapoptotic Bax genes, respectively. Using the DAF-FM DA fluorescence probe, compound 12b produced NO intracellularly as efficiently as the reference drug JS-K. In silico molecular docking studies showed a structural similarity through an overlay of 12b with sorafenib. Interestingly, the drug-likeness properties of compound 12b met the expectations of Pfizer’s rule for the design of new drug candidates. Therefore, this study presents a novel anticancer lead compound that is worthy of further investigation and activity improvement.

Accurate blood smear quantification with various blood cell samples is of great clinical importance. The conventional manual process of blood smear quantification is quite time consuming and is prone to errors. Therefore, this paper presents automatic detection of the most frequently occurring condition in human blood&mdash, microcytic hyperchromic anemia&mdash, which is the cause of various life-threatening diseases. This task has been done with segmentation of blood contents, i.e., Red Blood Cells (RBCs), White Blood Cells (WBCs), and platelets, in the first step. Then, the most influential features like geometric shape descriptors, Gray Level Co-occurrence Matrix (GLCM), Gray Level Run Length Matrix (GLRLM), and Gabor features (mean squared energy and mean amplitude) are extracted from each of the RBCs. To discriminate the cells as hypochromic microcytes among other RBC classes, scanning is done at angles (0∘, 45∘, 90∘, and 135∘). To achieve high-level accuracy, Adaptive Synthetic (AdaSyn) sampling for imbalance learning is used to balance the datasets and locality sensitive discriminant analysis (LSDA) technique is used for feature reduction. Finally, upon using these features, classification of blood cells is done using the multilayer perceptual model and random forest learning algorithms. Performance in terms of accuracy was 96%, which is better than the performance of existing techniques. The final outcome of this work may be useful in the efforts to produce a cost-effective screening scheme that could make inexpensive screening for blood smear analysis available globally, thus providing early detection of these diseases.