Evaluation of Biological Potency of two Endemic Species Integrated with in vitro and in silico Approches: LC-MS/MS Analysis of the Plants.

In the present study, the main phytochemical components of endemic plant extracts and inhibitory potency were screened related to different biological activities. Seven compounds were quantified, and cyanidin-3-o-glucoside was the dominant secondary metabolite in the extract of plants. The extract from P. asiae-minoris (PAM) exhibited the best enzyme inhibitory activity against BChE (1.73±0.23 µg mL-1 ), tyrosinase (2.47±0.28 µg mL-1 ), α-glucosidase (5.28±0.66 µg mL-1 ), AChE (8.66±0.86 µg mL-1 ), and ACE (19.27±1.02 µg mL-1 ). In vitro antioxidant assay, PAM extract possessed the highest activity in respect of DPPH radical scavenging (24.29±0.23 µg/mL), ABTS⋅+ scavenging (13.50±0.27 µg/mL) and FRAP reducing power (1.56±0.01 µmol TE/g extract). MIC values ranged from 1-8 mg/mL for antibacterial ability, and the PAM extract showed a stronger effect for B. subtilis, E. faecalis, and E. coli at 1 mg/mL. The antiproliferative ability of A. bartinense (AB) extract demonstrated a suppressive effect (IC50 : 70.26 µg/mL) for pancreatic cancer cell lines. According to the affinity scores analysis, the cyanidin-3-o-glucoside demonstrated the lowest docking scores against ACE, AChE, BChE, and collagenase. It was found that the PAM extract exhibited better inhibitory capabilities than A. bartinense. The P. asiae-minoris plant, reported to be in the Critically Endangered (CR) category, should be conserved by culturing, considering its biological abilities.

Heterocyclic compounds with different moieties: synthesis and evaluation of biological activities assisted with the computational study.

In the present work, heterocyclic compounds containing different moieties, such as pyrazole and thiophene, were synthesized and screened for inhibitory potency against medicinal enzymes and bacterial and cancer (breast and cervical) cell lines. The synthesized compounds have exhibited inhibitory capability against the studied enzymes. Among substances, C3 compound showed AChE and BChE inhibitory potency with the lowest IC50 value of 3.72 ± 0.57 and 1.66 ± 0.22 µM, respectively, in comparison to the standard tacrine. These analogs indicated varying degrees of tyrosinase inhibitory potencies ranging from 1.12 ± 0.50 to 7.70 ± 0.88 µM, and substance C4 was more potent against the enzyme than the reference compound, kojic acid. All four compounds have IC50 values between 37.11 ± 1.56-124.8 ± 2.09 µM for α-glucosidase. It was found that compound C1 exhibited a better antiproliferative activity compared to other substances, with IC50 values at 5.068 and 6.460 µg mL-1 for MCF-7 and HeLa cells, respectively. C1 and C2 compounds had good inhibitory ability against E. faecalis with a MIC value (16 µg mL-Ë¡). Molecular docking analysis showed that C3 has the lowest binding score against α-glucosidase (-8.617 kcal/mol).Communicated by Ramaswamy H. Sarma.

Accumulation of phenolic compounds and expression of phenylpropanoid biosynthesis-related genes in leaves of basil transformed with A. rhizogenes strains.

Biotic factors affect the content of secondary metabolites by interfering with molecular and biochemical pathways. In the current study, A. rhizogenes strains were inoculated into basil (Ocimum basilicum) to examine the effect of plant-microbe interaction on the accumulation of monomeric phenolic metabolites and the transcript levels of selected genes involved in the biochemical synthesis of secondary compounds. Initially, the integration of the rolB gene was validated by performing PCR analysis on genomic DNA samples from the basil plant inoculated with A. rhizogenes strains. We have detected that the accumulation of mRNA transcripts linked to the biosynthesis pathway of phenolic compounds has higher transcript expression levels in the leaves of transformed basil in proportion to uninoculated plants. Basil plants inoculated with A. rhizogenes 39207 strain had higher transcript levels of CAD, C4H, TAT, FLS, EGS, HPPR, PAL, and RAS genes than other experimental groups. We have identified eleven phenolic components, and the level of rosmarinic acid, eugenol, chicoric acid, and rutin increased in the inoculated basil leaves. However, the inoculation of A. rhizogenes did not cause a change in the compounds of chlorogenic acid, methyl chavicol, cinnamic acid, quercetin, vanillic acid, and caffeic acid. In conclusion, the increase in basic secondary metabolites could be achieved by the A. rhizogenes-mediated transformation of basil plants, and especially ATCC 43057 strain may be one of the A. rhizogenes strains. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01320-w.

A Silver Compound with Potential Applications as an Anticancer, Antibacterial, Antifungal, and Anti-Alzheimer's Agent.

This study investigated the biological activity of the silver coordination compound K-22. The IC50 values of K-22 on cancer cell lines range from 0.797 µg/mL to 3.426 µg/mL, indicating that K-22 might preferably inhibit A549, Saos-2, MCF-7, and HT-29 cell proliferation and thus have better therapeutic activity. Furthermore, K-22 stimulated apoptosis via up-regulation of the mRNA and protein expression level of Bax/Bcl-2 ratio in A549, Saos-2, MCF-7, and HT-29. K-22 exhibited antimicrobial activity against S. aureus, E. faecalis, K. pneumonia, P. aeruginosa, C. utilis, and C. albicans. Experimental results show that the compound has inhibitory potential with an IC50 value of 178.10 µM for the BChE (butyrylcholinesterase) enzyme, which has a vital role in the progression of Alzheimer's disease. As a result, compound K-22 exhibits a strong potential for medical use due to its anticancer, antibacterial, antifungal, and anti-Alzheimer properties.

Synthesis and evaluation of novel xanthene-based thiazoles as potential antidiabetic agents.

A series of xanthene-based thiazoles was synthesized and characterized by different scpectroscopic methods, i.e. Proton nuclear magnetic resonance (1 H NMR), carbon nuclear magnetic resonance (13 C NMR), infrared spectroscopy, carbon hydrogen nitrogen analysis, and X-ray crystallography. The inhibition potencies of 18 newly synthesized thiazole derivatives were investigated on the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), α-amylase (α-Amy), and α-glycosidase (α-Gly) enzymes in accordance with their antidiabetic and anticholinesterase ability. The synthesized compounds have the highest inhibition potential against the enzymes at low nanomolar concentrations. Among the 18 newly synthesized molecules, 3b and 3p were superior to the known commercial inhibitors of the enzymes and have a much more effective inhibitory potential, with IC50 : 2.37 and 1.07 nM for AChE, 0.98 and 0.59 nM for BChE, 56.47 and 61.34 nM for α-Gly, and 152.48 and 124.84 nM for α-Amy, respectively. Finally, the optimized 18 compounds were subjected to molecular docking to describe the interaction between thiazole derivatives and AChE, BChE, α-Amy, and α-Gly enzymes in which important interactions were monitored with amino acid residues of each target enzyme.

Turanecio hypochionaeus: Determination of Its Polyphenol Contents, and Bioactivities Potential Assisted with in Silico Studies.

The aim of this study was to identify and quantify the phenolic composition of Turanecio hypochionaeus Bosse and determine the anti-urease, anti-lipase, antidiabetic, anti-melanogenesis, antibacterial, and anti-Alzheimer properties. IC50 results for all enzymes were obtained between 0.234-116.50 µg/mL and this plant inhibited HMG_CoA R and glucosidase enzymes more with IC50 values of 0.234 and 116.50 µg/mL, respectively. Among the 11 secondary metabolites identified in T. hypochionaeus extract, chlorogenic acid 255.459±1.17 µg g-1 ), benzoic acid (56.251±1.98 µg g-1 ), and catechin (29.029±0.27 µg g-1 ) were determined as the most abundant phenolic compounds. According to the results of the tested microorganisms, the plant extracts showed antimicrobial and antifungal properties in a dose-dependent manner. In molecular docking study, the interactions of active compounds extracted from Turanecio hypochionaeus plant and showing activity against diverse metabolic enzymes were examined. The most active compound 1, (chlorogenic acid) has -12.80, -12.80, -12.60 and -12.00 kcal/mol binding energy value against HMG_CoA R, and α-amylase, α-glucosidase, and lipase, respectively.

Evaluation of synthetic 2-aryl quinoxaline derivatives as α-amylase, α-glucosidase, acetylcholinesterase, and butyrylcholinesterase inhibitors.

Variety of 2-aryl quinoxaline derivatives 1-23 were synthesized in good yields, by reacting 1,2-phenylenediamine with varyingly substituted phenacyl bromides in the presence of pyridine catalyst. All molecules 1-23 were characterized by spectroscopic techniques and evaluated for their diverse biological potential against α-amylase (α-AMY), α-glucosidase (α-GLU), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) enzymes. Synthetic derivatives possess enhanced inhibitory potential against all enzymes at nanomolar concentrations. In particular, compound 14 was found much superior with IC50 = 294.35, 198.21, 17.04, and 21.46 nM against α-AMY, α-GLU, AChE, and BChE, respectively, as compared to standard inhibitors. Furthermore, selected potent compounds, including 3, 4, 8, 14, 15, 17, and 18, were subjected to molecular docking studies to decipher the binding energies and interactions of ligands (synthetic molecules) with all four target enzymes.

Polyphenolic compounds: Synthesis, assessment of antimicrobial effect and enzymes inhibition against important medicinal enzymes with computational details.

Phenolic compounds mainly benefit human health and have many biological activities. Their activities are related to their structure, which allows them to interact with enzymes. The inhibition potencies of synthesized polyphenolic compounds (3a and 3b) were investigated on cholinesterases, α­Gly, and tyrosinase activities. The structures of 3a and 3b were determined based on spectral data (NMR, UV-vis, XRD pattern, SEM, and EDX). The compounds have effective inhibitory potential with IC50 value between 2.25 ± 0.35-5.66 ± 0.75 µM and Ki values 2.95 ± 0.37-14.86 ± 4.99 µM for AChE, BChE, and tyrosinase. It was determined that the synthesized compounds have biological activities by the MIC and cytotoxicity tests, and they have IC50 values of 16.15 µg/mL and 12.16 µg/mL for the PC-3 cell line, respectively. According to the calculated molecular docking results, these compounds showed the highest binding energy against AChE and tyrosinase enzymes (-11.3 and -10.4 kcal/mol, respectively). The compounds have synthetic accessibility scores of 2.75 and 4.55 based on the drug-likeness properties.

The interactive effect of aromatic amino acid composition on the accumulation of phenolic compounds and the expression of biosynthesis-related genes in Ocimum basilicum.

Sweet basil (Ocimum basilicum L.), a well-known medicinal and aromatic herb, rich in essential oils and antioxidants (contributed by phenolics), is widely used in traditional medicine. The biosynthesis of phytochemicals occurs via different biochemical pathways, and the expression of selected genes encoding enzymes involved in the formation of phenolic compounds is regulated in response to environmental factors. The synthesis of the compounds is closely interrelated: usually, the products formed in the first reaction steps are used as substrates for the next reactions. The current study attempted a comprehensive overview of the effect of aromatic amino acid composition (AAAs) in Ocimum basilicum in respect to the expression of genes related to the biosynthesis of phenolic compound and their content. The transcript expression levels of EOMT, PAL, CVOMT, HPPR, C4L, EGS, and FLS increased depending on the AAAs concentration compared to the control plants. The highest mRNA accumulation was obtained in EOMT, FLS, and HPPR in the leaves of sweet basil. The expression of the TAT gene in the leaves significantly reduced in response to all AAAs applications compared to untreated groups and it had the lowest transcript accumulation. Eleven individual phenolic compounds were determined in the basil leaves, and the contents of chicoric acid, methyl chavicol, caffeic acid, and vanillic acid increased depending on administered concentration to control (p < 0.05). Additionally, AAAs lead to an incremental change in the amount of chlorogenic acid at 50 and 100 mg kg-1 compared to control plants (p < 0.05). Rutin and rosmarinic acid were detected as the main phenolic compounds in all experimental groups of sweet basil in terms of quantity. However, their amount significantly decreased as compared to control plants based on the increase in AAAs concentrations (p < 0.05). Also, the accumulation of cinnamic acid, eugenol, and quercetin did not significantly change in the leaves of AAAs treated plants compared to control (p < 0.05). When AAAs was applied, total flavonoid content increased in all treatments compared to the control plants, but total phenolic content did not change significantly (p < 0.05). To the best of our knowledge, our work is the first detailed work to evaluate in detail the impact of AAAs on individual phenolic compounds at the phytochemistry and transcriptional levels in the O. basilicum plant. For a detailed understanding of the whole mechanism of phenolic compound regulation, further research is required to fill in some gaps and to provide further clarification.

Bioactivity and molecular docking studies of some nickel complexes: New analogues for the treatment of Alzheimer, glaucoma and epileptic diseases.

The interaction of the coordination compounds with biological molecules resulted in the investigation of the drug potential of these molecules. In this study, enzyme inhibition of DSA (1-3) coordination compounds that were previously investigated for their anticancer and antibacterial properties was investigated. Also, DSA (1-3) had Ki values of 635.30 + 152.62, 184.01 + 90.05, and 163.03 ± 60.01 µM against human carbonic anhydrase I, 352.23 ± 143.09, 46.2 ± 15.47, and 54.117 ± 18.80 µM against AChE, 310.64 ± 97.35, 35.54 ± 7.01, and 101.51 ± 15.314 µM against BChE, respectively. The biological activity values of these compounds against enzymes whose name are AChE, BChE, and hCAI were compared. Ellman and Verporte methods were used for the study of these enzymes. Cholinesterase inhibitors, also known as anti-cholinesterase and cholinesterase blocking drugs, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine. They may be used as drugs for Alzheimer's and myasthenia gravis. It is a common method for comparing biological activity values of nickel complexes with molecular docking calculations. Nickel complexes were studied against enzymes that are human carbonic anhydrase isozyme I for ID 2CAB (hCA I), butyrylcholinesterase for ID 1P0I (BChE), and acetylcholinesterase for ID 1EEA (AChE), respectively.

Statistical Assessment of Toxic and Essential Metals in the Serum of Female Patients with Lung Carcinoma from Pakistan.

Lung cancer (LC) is the number one cancer killer of women both in the USA and around the world. Besides cigarette smoking, an important feature in the etiology of LC is its strong association with exposure of toxic metals. The primary objective of the present investigation was to assess the concentrations of toxic/essential elements (Ni, Ca, Se, Zn, Co, K, Cr, As, Cu, Na, Fe, Hg, Cd, Mg, Mn, and Pb) in the serum samples of LC female patients with female controls by atomic absorption spectrometry after wet-acid digestion procedure. Carcinoembryonic antigen (CEA) was also measured in the serum of the patients using immunoradiometric method. Comparative appraisal of the data revealed that concentrations of Cr, Mg, Cd, Pb, Hg, As, and Ni were noted to be high significantly in serum of LC female patients, while the average Fe, Co, Mn, Na, K, Zn, Ca, and Se were observed at higher levels in female controls (p < 0.05). The correlation study revealed significantly different mutual associations among the elements in the both donor groups. Markedly, variations in the elemental levels were also noted for different types (non-small cell lung cancer and small cell lung cancer) and stages (I, II, III, & IV) of LC patients. Multivariate analyses showed substantially diverse apportionment of the metals in the female patients and female controls. Hence, present findings suggest that the toxic and essential metals accumulated in the body may pose a high risk for LC progression in Pakistani females.

Expression analysis of metallothioneins and mineral contents in tomato (Lycopersicon esculentum) under heavy metal stress.

BACKGROUND: Heavy metals are considered to be the most important pollutants in the contamination of soils; they adversely affect plant growth and development and cause some physiological and molecular changes. The contamination of agricultural soils by heavy metals has changed the mineral element content of vegetables. Plant metallothioneins (MTs) are thought to have the functional role in heavy metal homeostasis, and they are used as the biomarkers for evaluating environmental pollution. We aimed to evaluate the expression of MT isoforms (MT1, 2, 3 and 4) and some mineral element composition of tomato roots, leaves and fruits exposed to copper and lead. RESULTS: Heavy metal applications increased MT1 and MT2 gene expressions compared to the control in the tissues of tomato. The highest level of MT1 and MT2 transcripts was found in roots and leaves, respectively. The expression of MT3 is induced in roots, leaves and fruits except for Pb treatment in roots. MT4 expression increased in fruits; however, other tissues did not show a clear change. Our results indicated that Cu content was higher than Pb in all tissues of tomato. The lower doses of Cu (10 ppm) increased the content of Mg, Fe, Ca and Mn in roots. Pb generally increased the level of minerals in leaves and fruits, but it decreased Mg, Mn and Fe contents in roots. CONCLUSION: Both heavy metals not only moved to aerial parts but also caused alterations to mineral element levels. These results show that MT transcripts are regulated by Cu and Pb, and expression pattern changes to MT isoforms and tissue types. © 2016 Society of Chemical Industry.

Gene expression analysis of metallothionein and mineral elements uptake in tomato (Solanum lycopersicum) exposed to cadmium.

Heavy metals such as Cd are considered to be the most important pollutants in soil contamination. Cd is a non-essential element adversely affecting plant growth and development, and it has caused some physiological and molecular changes. Metallothioneins (MTs) are low molecular weight, cysteine-rich, and metal binding proteins. In this study, we aimed to evaluate the MT gene expression levels and minerals uptake in the tissues of Solanum lycopersicum exposed to Cd. The transcriptional expression of the MT genes was determined by real-time quantitative PCR. The MT genes were regulated by the Cd and the mineral elements uptake changed tissue type and applied doses. The MT1 and MT2 transcript levels increased in the roots, the leaves and the fruits of the tomato. The MT3 and MT4 transcript pattern changed according to the tissue types. The Cd treatment on the growth medium increased the Mg, Ca, and Fe content in both the leaves and fruits of the tomato. However, the Cd affected the mineral levels in the roots depending on the mineral types and doses. Also, the Cd content increased in the roots, the leaves, and the fruits of the tomato, respectively. The results presented in this study show that Cd has synergistic and/or antagonistic effects on minerals depending on the tissue types. These results indicate that the MT1 and MT2 expression pattern increased together with the Mg, Ca, and Fe content in both the leaves and the fruits of the tomato.