Computer-aided identification of Mycobacterium tuberculosis resuscitation-promoting factor B (RpfB) inhibitors from Gymnema sylvestre natural products.

Tuberculosis (TB), an infectious disease caused by multi-drug resistant Mycobacterium tuberculosis (Mtb), has been a global health concern. Mtb affects over a third of the world's population, causing two million deaths annually due to its dormancy and propensity to spread infection during this period. Resuscitation-promoting factor B (RpfB) plays a pivotal role in the growth of Mtb during dormant periods, making it a critical target for eliminating Mtb and curing TB. Gymnema sylvestre is a famous medicinal plant with several medicinal properties, including antimicrobial activity; however, the therapeutic potential of the various reported metabolites of this plant against Mtb has not yet been explored. The aim of this study was to explore the reported natural products of G. sylvestre against the RpfB of the Mtb. A total of 131 reported secondary metabolites of this plant were collected and virtually screened against the RpfB. We particularly targeted the Glu292 residue of RpfB as it is crucial for the catalysis of this protein. From our in-house library, 114 compounds showed a binding affinity higher than the standard drug. The binding stability of the top three lead compounds was further confirmed through MD simulation analysis. Drug likeness analyses indicated that the ten hits had zero violations of the Lipinski rule of five. In addition, analyses of pharmacokinetics, toxicity, and target prediction revealed that the top compounds are devoid of toxicity and do not affect human proteins. Additionally, they reflect multifaceted approach as anti-TB agents. Our selected hits not only exhibit molecular properties favoring physiological compatibility but also exhibit properties enhancing their potential efficacy as therapeutic candidates. The compounds investigated here are worthy of experimental validation for the discovery of novel treatments against TB. Further, this study also provides a promising avenue for research on the pharmacological potential of G. sylvestre.

Cobalt oxide modified sulfur and phosphorus Co-doped g-C3N4 for screening of urinary human albumin.

The fabrication of a heteroatom-doped nanocomposite based on cobalt oxide modified sulfur, phosphorus co-doped carbon nitride (Co3O4/SP-CN) with increased active sites is reported. The synthesized nanocomposite offers surprisingly high electrocatalytic oxidation efficacy toward human albumin (HA) despite its agglomeration. This improved efficacy of Co3O4/SP-CN nanocomposite could be attributed to its increased adsorption sites and surface defects, fast charge transportation capability, and conductivity. Additionally, morphological and compositional analysis of the fabricated Co3O4/SP-CN material has been performed  through scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photon spectroscopy (XPS), and Raman spectroscopy. The fabricated electrode shows remarkable amperometric response against the HA with a limit of detection of 8.39 nM and linear range of 20-4000 nM at applied potential of 0.25 V versus Ag/AgCl in 0.1 M PBS (pH 8.2). The designed Co3O4/SP-CN electrode has been successfully applied to monitor HA in  urine samples of diabetic patient with recovery percentage from 94.1 and 92.1% and with relative standard deviation (RSD) values of 5.8 and 7.8%. According to the best of our knowledge, this is the first report to use a Co3O4/SP-CN-based graphitic pencil (GP) electrode for monitoring of HA for early diagnosis of diabetic nephropathy.

Isolation, Structure Elucidation and In Silico Prediction of Potential Drug-Like Flavonoids from Onosma chitralicum Targeted towards Functionally Important Proteins of Drug-Resistant Bad Bugs.

Admittedly, the disastrous emergence of drug resistance in prokaryotic and eukaryotic human pathogens has created an urgent need to develop novel chemotherapeutic agents. Onosma chitralicum is a source of traditional medicine with cooling, laxative, and anthelmintic effects. The objective of the current research was to analyze the biological potential of Onosma chitralicum, and to isolate and characterize the chemical constituents of the plant. The crude extracts of the plant prepared with different solvents, such as aqueous, hexane, chloroform, ethyl acetate, and butanol, were subjected to antimicrobial activities. Results corroborate that crude (methanol), EtoAc, and n-C6H14 fractions were more active against bacterial strains. Among these fractions, the EtoAc fraction was found more potent. The EtoAc fraction was the most active against the selected microbes, which was subjected to successive column chromatography, and the resultant compounds 1 to 7 were isolated. Different techniques, such as UV, IR, and NMR, were used to characterize the structures of the isolated compounds 1-7. All the isolated pure compounds (1-7) were tested for their antimicrobial potential. Compounds 1 (4',8-dimethoxy-7-hydroxyisoflavone), 6 (5,3',3-trihydroxy-7,4'-dimethoxyflavanone), and 7 (5',7,8-trihydroxy-6,3',4'-trimethoxyflavanone) were found to be more active against Staphylococcus aureus and Salmonella Typhi. Compound 1 inhibited S. typhi and S. aureus to 10 ± 0.21 mm and 10 ± 0.45 mm, whereas compound 6 showed inhibition to 10 ± 0.77 mm and 9 ± 0.20 mm, respectively. Compound 7 inhibited S. aureus to 6 ± 0.36 mm. Compounds 6 and 7 showed significant antibacterial potential, and the structure-activity relationship also justifies their binding to the bacterial enzymes, i.e., beta-hydroxyacyl dehydratase (HadAB complex) and tyrosyl-tRNA synthetase. Both bacterial enzymes are potential drug targets. Further, the isolated compounds were found to be active against the tested fungal strains. Whereas docking identified compound 7, the best binder to the lanosterol 14α-demethylase (an essential fungal cell membrane synthesizing enzyme), reported as an antifungal fluconazole binding enzyme. Based on our isolation-linked preliminary structure-activity relationship (SAR) data, we conclude that O. chitralicum can be a good source of natural compounds for drug development against some potential enzyme targets.

Antidiabetic activities of alkaloids isolated from medicinal plants

Diabetes mellitus is a metabolic disorder affecting a great part of population around the world. It is the fifth leading death causing disease in the world and its cases are increasing day by day. Traditional medicine is thought to have promising future in the treatment of diabetes mellitus. In contrast to synthetic drugs phytochemicals are considered to be free from side effects. As one of the main class of natural products, alkaloids and their derivatives have been widely used as sources of pharmacological agents against a variety of medical problems. Many studies confirmed the role of alkaloids in the management of diabetes and numerous alkaloids isolated from different medicinal plants were found active against diabetes. Like other natural products, alkaloids regulate glucose metabolism either by inhibiting or inducing multiple candidate proteins including AMP-activated protein kinase, glucose transporters, glycogen synthase kinase-3, sterol regulatory element-binding proteins 1, glucokinase, glucose-6-phosphatase, acetyl-CoA carboxylase among the others. A comprehensive review of alkaloids reported in the literature with anti-diabetic activities and their target enzymes is conducted, with the aim to help in exploring the use of alkaloids as anti-diabetic agents. Future work should focus on rigorous clinical studies of the alkaloids, their development and relevant drug targets.

In-Depth Proteome Analysis of Ricinus communis Pollens.

Pollen grains are tiny structures vital for sexual reproduction and consequently seed and fruit production in angiosperms, and a source of many allergenic components responsible for deleterious implications for health worldwide. Current pollen research is mainly focused on unraveling the molecular mechanisms underlying the pollen germination and tube formation passing from the quiescent stage. In this context, an in-depth proteome analysis of the pollens from Ricinus communis at three different stages-that is, mature, hydrated, and in vitro germinated-is performed. This analysis results in the identification of 1950 proteins, including 1773, 1313, and 858, from mature, hydrated, and germinated pollens, respectively. Based on label-free quantification, 164 proteins are found to be significantly differentially abundant from mature to hydrated pollens, 40 proteins from hydrated to germinated, and 57 proteins from mature to germinated pollens, respectively. Most of the differentially abundant proteins are related to protein, carbohydrate, and energy metabolism and signaling. Besides other functional classes, a reasonable number of the proteins are predicted to be allergenic proteins, previously undiscovered. This is the first in-deep proteome analysis of the R. communis pollens and, to the best of our knowledge, one of the most complete proteome dataset identified from the pollens of any plant species, thus providing a reference proteome for researchers interested in pollen biology.

Chemical composition and antioxidant activity of certain Morus species.

In the present work, the fruits of four Morus species, namely Morus alba (white mulberry), Morus nigra (black mulberry), Morus laevigata (large white fruit), and Morus laevigata (large black fruit), were analyzed for proximate composition, essential minerals, and antioxidant potentials. For this purpose, the ripe fruits were collected from the northern regions of Pakistan. The major nutritional components (moisture, ash, lipids, proteins, fibres, carbohydrates, and total sugar) were found to be in the suitable range along with good computed energy. Total dry weight, pH, and titratable acidity (percent citric acid) were (17.60±1.94)-(21.97±2.34) mg/100 g, (3.20±0.07)-(4.78±0.15), and (0.84±0.40)%-(2.00±0.08)%, respectively. Low riboflavin (vitamin B(2)) and niacin (vitamin B(3)) contents were recorded in all the fruits, while ascorbic acid (vitamin C) was in the range from (15.20±1.25) to (17.03±1.71) mg/100 g fresh weight (FW). The mulberry fruits were rich with regard to the total phenol and alkaloid contents, having values of (880±7.20)-(1650±12.25) mg/100 g FW and (390±3.22)-(660±5.25) mg/100 g FW, respectively. Sufficient quantities of essential macro-(K, Ca, Mg, and Na) and micro-(Fe, Zn, and Ni) elements were found in all the fruits. K was the predominant element with concentration ranging from (1270±9.36) to (1731±11.50) mg/100 g, while Ca, Na, and Mg contents were (440±3.21)-(576±7.37), (260±3.86)-(280±3.50), and (240±3.51)-(360±4.20) mg/100 g, respectivly. The decreasing order of micro-minerals was Fe>Zn>Ni. The radical scavenging activity of methanolic extract of fruits was concentration-dependent and showed a correlation with total phenolic constituents of the respective fruits. Based on the results obtained, mulberry fruits were found to serve as a potential source of food diet and natural antioxidants.