Liquid chromatography-tandem mass spectrometry profile and antioxidant, antimicrobial, antiproliferative, and enzyme activities of Thymus pectinatus and Thymus convolutus: in vitro and in silico approach.

BACKGROUND: The objective of this study is to investigate the antiproliferative, antioxidant, antimicrobial, and enzyme activity capacities and phytochemical compositions of Thymus pectinatus (TP), Thymus convolutus (TC), which are endemic to Türkiye. Quantitative analysis of phenolic compounds in the extracts was conducted using liquid chromatography-tandem mass spectrometry, targeting 53 phenolic compounds. RESULTS: Rosmarinic acid, quinic acid, and cynaroside were identified as the major compounds, exhibiting quantitative variation in both extracts. The extracts had a high total phenolic content, with 113.57 ± 0.58 mg gallic acid equivalents (GAE)/g extract for TP and 130.52 ± 1.05 mg GAE/g extract for TC. Furthermore, although both extracts exhibited high total flavonoid content; the TP extract (75.12 ± 1.65 mg quercitin equivalents (QE)/g extract) displayed a higher flavonoid content than the TC extract (30.24 ± 0.74 mg QE/g extract) did. The extracts had a promising antiproliferative effect on C6, HeLa, and HT29 cancer cell lines with a less cytotoxic effect (10.5-14.2%) against normal cells. Both extracts exhibited very potent inhibitory activity against the xanthine oxidase enzyme, with half-maximal inhibitory concentration values of respectively 2.07 ± 0.03 µg mL-1 and 2.76 ± 0.06 µg mL-1 and moderate activity against tyrosinase and α-glucosidase. Docking simulations proved that rosmarinic acid and cynaroside, the major components of the extracts, were the most potent inhibitors of xanthine oxidase. According to antimicrobial activity results, the TC extract exhibited moderate activity against Staphylococcus aureus, and the TP extract had strong activity against both Enterococcus faecium and S. aureus. CONCLUSION: These findings emphasize the beneficial effects of the two endemic Thymus species on human health and suggest their potential use as plant-derived bioactive agents. © 2024 Society of Chemical Industry.

Centaurea mersinensis phytochemical composition and multi-dimensional bioactivity properties supported by molecular modeling.

Various studies conducted on Centaurea species indicate that the relevant plant is good source of bioactive phytochemicals. In this study, in vitro studies were used to determine bioactivity properties of methanol extract of Centaurea mersinensis - endemic species in Turkey - on extensive basis. Furthermore, the interaction of target molecules, identified for breast cancer and phytochemicals in the extract, was investigated via in silico analyses to support findings received in vitro. Scutellarin, quercimeritrin, chlorogenic acid and baicalin were primary phytochemicals in the extract. Methanol extract and scutellarin had higher cytotoxic effects against MCF-7 (IC50=22.17 µg/mL, and IC50=8.25 µM, respectively), compared to other breast cancer cell lines (MDA-MB-231, SKBR-3). The extract had strong antioxidant properties and inhibited target enzymes, especially α-amylase (371.69 mg AKE/g extract). The results of molecular docking indicate that main compounds of extract show high-strength bonding to the c-Kit tyrosine among target molecules identified in breast cancer, compared to other target molecules (MMP-2, MMP-9, VEGFR2 kinase, Aurora-A kinase, HER2). The tyrosinase kinase (1T46)-Scutellarin complex showed considerable stability in 150 ns simulation as per MD findings, and it was coherent with optimal docking findings. Docking findings and HOMO-LUMO analysis results corresponds with in vitro experiments. Medicinal properties of phytochemicals, which was determined to be suitable for oral use along with ADMET, were found to be within normal limits except for their polarity properties. In conclusion, in vitro and in silico studies indicated that the relevant plant yields promising results regarding its potential to develop novel and effective medicational products.Communicated by Ramaswamy H. Sarma.

Natural flavonoids as promising 6-phosphogluconate dehydrogenase inhibitor candidates: In silico and in vitro assessments.

The primary strategy in the fight against cancer is to screen compounds that may be effective on different types of cancer. Compounds from plants seem to be a good source. The present study investigated the inhibitory effects of some flavonoids on the 6-phosphogluconate dehydrogenase (6-PGD) enzyme. We determined that quercetin, myricetin, fisetin, morin, apigenin, and baicalein exhibited powerful inhibition effects with IC50 values between 4.08 and 21.26 µM, while luteolin, kaempferol, apiin, galangin, and baicalin showed moderate effects with IC50 values between 54.15 and 138.91 µM. Quercetin competitively inhibited the binding of NADP and 6-phosphogluconate to the 6-PGD enzyme with Ki values of 0.527 ± 0.251 and 0.374 ± 0.138 µM, respectively. We calculated Ki values using the Cheng-Prusoff equation as between 0.44 and 14.88 µM. The possible interaction details of polyphenols with the active site of 6-PGD were analyzed with docking software. In silico and in vitro studies indicated that the -OH groups on the A and C ring of flavonoids bind to the enzyme's active site via hydrogen bonding, while the -OH groups on the C ring contributed significantly to the increase in the inhibitory potentials of the molecules. Molecular dynamic simulations tested the stability of the 6-PGD-quercetin complex during 100 ns. These phytochemicals were suitable for drug use when optimized with absorption, distribution, metabolism, excretion, and toxicity (ADMET) criteria. The effects of the studied compounds on cancer cell lines of potential targets were demonstrated by network analysis. In conclusion, this study suggests that flavonoids found to be potent inhibitors could serve as leading candidates to treat many cancers via 6-PGD inhibition.

Biological Effects and Crystal X-Ray Study of Novel Schiff Base Containing Pentafluorophenyl Hydrazine: In Vitro and in Silico Studies.

A novel Schiff base namely 3,5-di-tert-butyl-6-((2-(perfluorophenyl)hydrazono)methyl)phenol was successfully synthesized and characterized using FT-IR and 1 H-NMR, 13 C-NMR, and 19 F-NMR. The crystal structure analysis of the Schiff base compound was also characterized with single crystal X-ray diffraction studies and supported the spectroscopic results. The cytotoxicity, anti-bacterial properties, and enzyme inhibition of the compound were also investigated. The molecular docking studies were performed in order to explain the interactions of the synthesized compound with target enzymes. The newly synthesized hydrazone derivative Schiff base compound showed high cellular toxicity on MCF-7 and PC-3 cells. Also, this compound caused low antibacterial effect on E. coli and S. aureus. Besides, the compound exhibited the inhibitory effect against pancreatic cholesterol esterase and carbonic anhydrase isoenzyme I, II with IC50 values 63, 99, and 188 µM, respectively. Consequently, it has been determined that the prepared Schiff base is an active compound in terms of cytotoxicity, enzyme inhibition, and anti-bacterial properties. These results provide preliminary information for some biological features of the compound and can play a major role in drug applications of the Schiff base compound.

Investigation of α-glucosidase and α-amylase inhibitory effects of phenoxy chalcones and molecular modeling studies.

Diabetes mellitus is one of the most critical health problems affecting the quality of life of people worldwide, especially in developing countries. According to the World Health Organization reports, the number of patients with diabetes is approximately 420 million, and this number is estimated to be 642 million in 2040. There are 2 main types of diabetes: Type 1 (T1DM), where the body cannot produce enough insulin, and Type 2 (T2DM), where the body cannot use insulin properly. Patients with T1DM are treated with insulin injections while oral glucose-lowering drugs are used for patients with T2DM. Oral antihyperglycemic drugs used in the treatment of type 2 diabetes mellitus have different mechanisms. Among these, α-Glucosidase and α-amylase inhibitors are one of the most important inhibitors. The antidiabetic effect of the chalcones, which show rich activity, draws attention. This research aims to synthesize chalcone derivatives that could show potential antidiabetic activity. In this study, the inhibitory activity of the chalcone compounds (4a-4g, 5a-5g) was tested against α-glucosidase and α-amylase enzymes. Besides, molecular modeling was utilized to predict potential interactions of the synthesized compounds that exhibit inhibitory effects. In both in vitro and in silico studies, the analyses revealed that compound 5e exhibits strong inhibitory effects against α-glucosidase enzymes (Binding energy: -7.75 kcal/mol, IC50 : 28.88 µM). Additionally, compound 4f demonstrates encouraging inhibitory effects against α-Amylase (Binding energy: -11.08 kcal/mol, IC50 : 46. 21 µM).

Bio-Oriented Synthesis and Molecular Docking Studies of 1,2,4-Triazole Based Derivatives as Potential Anti-Cancer Agents against HepG2 Cell Line.

Triazole-based acetamides serve as important scaffolds for various pharmacologically active drugs. In the present work, structural hybrids of 1,2,4-triazole and acetamides were furnished by chemically modifying 2-(4-isobutylphenyl) propanoic acid (1). Target compounds 7a-f were produced in considerable yields (70-76%) by coupling the triazole of compound 1 with different electrophiles under different reaction conditions. These triazole-coupled acetamide derivatives were verified by physiochemical and spectroscopic (HRMS, FTIR, 13CNMR, and 1HNMR,) methods. The anti-liver carcinoma effects of all of the derivatives against a HepG2 cell line were investigated. Compound 7f, with two methyl moieties at the ortho-position, exhibited the highest anti-proliferative activity among all of the compounds with an IC50 value of 16.782 µg/mL. 7f, the most effective anti-cancer molecule, also had a very low toxicity of 1.190.02%. Molecular docking demonstrates that all of the compounds, especially 7f, have exhibited excellent binding affinities of -176.749 kcal/mol and -170.066 kcal/mol to c-kit tyrosine kinase and protein kinase B, respectively. Compound 7f is recognized as the most suitable drug pharmacophore for the treatment of hepatocellular carcinoma.

Assessment of Anticholinergic and Antidiabetic Properties of Some Natural and Synthetic Molecules: an In Vitro and In Silico Approach.

INTRODUCTION: In this study, it was aimed to determine the in vitro and in silico effects of some natural and synthetic molecules on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase enzymes. BACKGROUND: Alzheimer's disease (AD) and Type II diabetes mellitus (T2DM), which are considered amongst the most important diseases of today's world. However, the side effects of therapeutic agents used in both diseases limit their use. Therefore, it is important to develop drugs with high therapeutic efficacy and better pharmacological profile. OBJECTIVE: This study sets out to determine the related enzyme inhibitors used in the treatment of AD and T2DM, which are considered amongst the most important diseases of today's world. METHODS: In the current study, the in vitro and in silico effects of dienestrol, hesperetin, L-thyroxine, 3,3',5-Triiodo-L-thyronine (T3) and dobutamine molecules on AChE, BChE and α-glycosidase enzyme activities were investigated. RESULTS: All the molecules showed an inhibitory effect on the enzymes. The IC50 and Ki values of the L-Thyroxine molecule, which showed the strongest inhibition effect for the AChE enzyme, were determined as 1.71 µM and 0.83±0.195 µM, respectively. In addition, dienestrol, T3 and dobutamine molecules showed a more substantial inhibition effect than tacrine. Dobutamine molecule showed the most substantial inhibition effect for BChE enzyme, and IC50 and Ki values were determined as 1.83 µM and 0.845±0.143 µM, respectively. The IC50 and Ki values for the hesperetin molecule, which showed the strongest inhibition for the α-glycosidase enzyme, were determined as 13.57 µM and 12.33±2.57 µM, respectively. CONCLUSION: According to the results obtained, it may be said that the molecules used in the study are potential inhibitor candidates for AChE, BChE and α-glycosidase.

Synthesis, characterizations of aryl-substituted dithiodibenzothioate derivatives, and investigating their anti-Alzheimer's properties.

The main objective of the present study was to synthesize potential inhibitor/activators of AChE and hCA I-II enzymes, which are thought to be directly related to Alzheimer's disease. Dithiodibenzothioate compounds were synthesized by thioesterification. Six different thiolate compounds produced were characterized by 1H-, 13C-NMR, FT-IR, LC-MS/MS methods. HOMO-LUMO calculations and electronic properties of all synthesized compounds were comprehensively illuminated with a semi-empirical molecular orbital (SEMO) package for organic and inorganic systems using Austin Model 1 (AM1)-Hamiltonian as implemented in the VAMP module of Materials Studio. In addition, the inhibition effects of these compounds for AChE and hCA I-II in vitro conditions were investigated. It was revealed that TE-1, TE-2, TE-3, TE-4, TE-5, and TE-6 compounds inhibited the AChE under in vitro conditions. TE-1 compound activated the enzyme hCA I while TE-2, TE-3 TE-4 compounds inhibited it. TE-5 and TE-6, on the other hand, did not exhibit a regular inhibition profile. Similarly, TE-1 activated the hCA II enzyme whereas TE-2, TE-3, TE-4, and TE-5 compounds inhibited it. TE-6 compound did not have a consistent inhibition profile for hCA II. Docking studies were performed with the compounds against AChE and hCA I-II receptors using induced-fit docking method. Molecular Dynamics (MD) simulations for best effective three protein-ligand couple were conducted to explore the binding affinity of the considered compounds in semi-real in-silico conditions. Along with the MD results, TE-1-based protein complexes were found more stable than TE-5. Based on these studies, TE-1 compound could be considered as a potential drug candidate for AD.Communicated by Ramaswamy H. Sarma.

Identification of Natural Compounds as Inhibitors of Pyruvate Kinase M2 for Cancer Treatment.

The reliance of tumor cells on aerobic glycolysis is one of the emerging hallmarks of cancer. Pyruvate kinase M2 (PKM2), an important enzyme of glycolytic pathway, is highly expressed in a number of cancer cells. Tumor cells heavily depend on PKM2 to fulfill their divergent energetic and biosynthetic requirements, suggesting it as novel drug target for cancer therapies. Based on this context, we performed enzymatic-assay-based screening of the in-house phenolic compounds library for the identification of PKM2 inhibitors. This screening identified silibinin, curcumin, resveratrol, and ellagic acid as potential inhibitors of PKM2 with IC50 values of 0.91 µM, 1.12 µM, 3.07 µM, and 4.20 µM respectively. For the determination of Ki constants and the inhibition type of hit compounds, Lineweaver-Burk graphs were plotted. Silibinin and ellagic acid performed the competitive inhibition of PKM2 with Ki constants of 0.61 µM and 5.06 µM, while curcumin and resveratrol were identified as non-competitive inhibitors of PKM2 with Ki constants of 1.20 µM and 7.34 µM. The in silico screening of phenolic compounds against three binding sites of PKM2 provided insight into the binding pattern and functionally important amino residues of PKM2. Further, the evaluation of cytotoxicity via MTT assay demonstrated ellagic acid as potent inhibitor of cancer cell growth (IC50 = 20 µM). These results present ellagic acid, silibinin, curcumin, and resveratrol as inhibitors of PKM2 to interrogate metabolic reprogramming in cancer cells. This study has also provided the foundation for further research to validate the potential of identified bioactive entities for PKM2 targeted-cancer therapies.

Multidimensional in silico strategy for identification of natural polyphenols-based SARS-CoV-2 main protease (Mpro) inhibitors to unveil a hope against COVID-19.

SARS-CoV-2, a rapidly spreading new strain of human coronavirus, has affected almost all the countries around the world. The lack of specific drugs against SARS-CoV-2 is a significant hurdle towards the successful treatment of COVID-19. Thus, there is an urgent need to boost up research for the development of effective therapeutics against COVID-19. In the current study, we investigated the efficacy of 81 medicinal plant-based bioactive compounds against SARS-CoV-2 Mpro by using various in silico techniques. The interaction affinities of polyphenolic compounds towards SARS-CoV-2 Mpro was assessed via intramolecular (by Quantum Mechanic), intermolecular (by Molecular Docking), and spatial (by Molecular Dynamic) simulations. Our obtained result demonstrate that Hesperidin, rutin, diosmin, and apiin are most effective compounds agents against SARS-CoV-2 Mpro as compared to Nelfinavir (positive control). This study will hopefully pave a way for advanced experimental research to evaluate the in vitro and in vivo efficacy of these compounds for the treatment of COVID-19.

Characterization of highly stable extracellular lipase from the extremely halophilic archaeon Halolamina sp

Enzymes of the archaea living in extreme environments are resistant to the challenging conditions. Lipase is among the important enzymes used in the industry and agriculture. In this study, the extracellular lipase from extremely halophilic archaeon Halolamina sp. was characterized for the first time. Optimum temperature for the enzyme activity was determined as 70oC, optimum pH was 7.0, and the optimum salt concentration was 3.6 M. Additionally, more than 70% of the enzyme activity was remained between pH 3.0-10.0 for 48 h as well as incubation of the enzyme at 70oC for 30 min increased its activity for 44%, and no activity loss was observed after incubation at 80oC. Also, presence of the metals increased the enzyme activity up to 88%. The enzyme was highly resistant to the organic solvents acetone, methanol, and DMSO while strong inhibition was caused by n-butanol. Among the detergents, the enzyme kept its activity substantially in the presence of SDS; however, other detergents caused inhibition of the enzyme activity. This characterization study showed that the lipase from the haloarchaeon Halolamina sp. is highly stable at the wide ranges of temperature and pH values as well as in the presence of diverse inhibitors. This enzyme is promising to be used in biotechnological applications.

Screening inhibitory effects of selected flavonoids on human recombinant aldose reductase enzyme: in vitro and in silico study.

Aldose reductase (AR) is the first enzyme of the polyol pathway that has physiological importance under hyperglycaemic conditions. The article has been focussed on AR enzyme inhibition by selected compounds. For this purpose, the in vitro inhibitory effects of various compounds on commercially available recombinant human AR (rAR) enzyme activity were investigated. The IC50 values of compounds on rAR inhibition effect were found for 6-hydroxy flavone, syringic acid, diosmetin, 6-fluoroflavone, 7-hydroxy-4'-nitroisoflavone, myricetin as 2.05, 2.97, 15.75, 16.1, 49.5, and 63 µM, respectively. 6-Hydroxy flavone and syringic acid competitively inhibited rAR with respect to the NADPH with Ki values 0.509 ± 0.036 and 0.842 ± 0.012 µM. In addition, docking studies were performed to evaluate the potential enzyme binding positions of the compounds. Our in vitro and in silico results indicated that the 6-hydroxy flavone may be a good lead compound in the development of AR inhibitors to prevent diabetic complications.

Enhancing bactericidal strategy with selected aromatic compounds: in vitro and in silico study.

ß-Lactamases are enzymes that catalyze the hydrolysis of the ß-lactam ring, resulting in loss of function in ß-lactam antibiotics. In this report, the inhibition of ß-lactamase enzyme by group-based selected aromatic compounds, especially containing flavone ring, was investigated in vitro and in silico. For this purpose, the inhibitory effects of 7-hydroxy-4'-nitroisoflavone, myricetin, formononetin, 3-methylflavone-8-carboxylic acid, 6-fluoroflavone and caffeic acid on ß-lactamase from Bacillus cereus enzyme activity were investigated. IC50 values of these compounds were determined to range from 53 to 346 mM. 7-hydroxy-4'-nitroisoflavone, formononetin and myricetin inhibited the enzyme with the Ki values of 27.65 ± 4.22, 58.92 ± 12.83 and 67.42 ± 5.77 µM, respectively. To evaluate the potential enzyme binding positions of the active compounds, docking studies were performed. In addition to kinetic and in silico studies, the synergistic effects of the compounds with penicillin on Klebsiella pneumoniae (ATCC 700603) and Escherichia coli (ATCC 35128) were tested in vitro. Our results indicated that 7-hydroxy-4'-nitroisoflavone, 3-methylflavone-8-carboxylic acid and myricetin that combined with penicillin completely precluded the bacterial growth.Communicated by Ramaswamy H. Sarma.

Synthesis, characterization, molecular docking and in vitro screening of new metal complexes with coumarin Schiff base as anticholine esterase and antipancreatic cholesterol esterase agents.

In this work, Combining coumarin and thiazole with 3-tertiary butyl salicylaldehyde into in a single molecule, new Schiff base (CTS), and its metal complexes with palladium and platinum were synthesized and characterized by using well-known spectroscopic techniques such as 1H-NMR, 13C-NMR, FT-IR and LC-MS. And also, the formation of these complexes were confirmed by magnetic moment and conductivity measurements. The photophysical properties of CTS were studied and it was observed that the Schiff base has a sensitivity to CN-, F-, and AcO- anions. The quantum chemical calculations based on density functional theory (DFT) were done for explaining some experimental, structural, and spectroscopic data of the dyes. Also, to evaluate the binding interactions between the ligand (CTS) and its metal complexes and enzymes, molecular docking studies were performed and all the compounds tested to determine its inhibition potential against the cholinesterase (AChE and BChE) and pancreatic cholesterol esterase (CEase) enzymes. Both in vitro and in silico the results showed that all of the compounds could act as potent inhibitors of AChE, BChE, and CEase. The Pt (II) complex showed the most potent inhibitory property against all of the enzymes with IC50 values of 12 µM for AChE, 23 µM for BChE, and 21 µM for CEase.Communicated by Ramaswamy H. Sarma.

Investigation of in vitro and in silico effects of some novel carbazole Schiff bases on human carbonic anhydrase isoforms I and II.

Carbonic anhydrases (CAs, EC4.2.1.1) are metalloenzymes that catalyse reversible hydration reaction of carbon dioxide to bicarbonate and protons. In recent years, there has been a great interest in inhibitors/activators of carbonic anhydrase isoenzymes. Therefore, we investigated the effects of four different carbazole Schiff base derivatives, which are believed to have a potential to be used as a drug, on human carbonic anhydrase (hCA) isoenzymes I and II under in vitro conditions. The IC50 values of carbazole Schiff base derivatives were found to be in the range of 32.09-151.2 µM for hCA isoenzyme I and 21.82-40.54 µM for hCA isoenzyme II. Among all compounds, (E)-3-(((9-Octyl-9H-carbazole-3-yl)imino)methyl)benzene-1,2-diol (C3) had the strongest inhibitory effect on hCA isoenzyme II. It was determined that 2,3,4-trimethoxy and 4-hydroxy phenyl containing carbazole compounds have selective inhibition against hCA II isoenzyme. Docking studies were performed against hCA I and II receptors using induced-fit docking method. The compounds had affinity scores varying from -7.74 ± 0.27 to -6.27 ± 0.07 kcal/mol for hCA I and from -8.04 ± 0.17 to -7.27 ± 0.18 kcal/mol for hCA II.Communicated by Ramaswamy H. Sarma.

A Review on Phyto-pharmacology of Oxalis corniculata.

Oxalis corniculata (Oxalidaceae) is a small decumbent and delicate appearing medicinal herb flourishing in warm temperate and tropical domains such as Pakistan and India. Main bioactive chemical constituents of Oxalis plant include several alkaloids, flavonoids, terpenoids, cardiac glycosides, saponins, and phlobatannins, along with steroids. Due to its polyphenolic, glycosides and flavonoid profile, it is proved to be protective in numerous ailments and exhibit various biological activities such as anti-fungal, anti-cancer, anti-oxidant, antibacterial, anti-diabetic, and cardioprotective. Moreover, bioactive phytochemicals from this plant possess significant wound healing potential. Our current effort intends to emphasize on the immense significance of this plant species, which have not been the subject matter of clinical trials and effective pharmacological studies, even though its favored usage has been stated. This review proposes that Oxalis corniculata possess a potential for the cure of various diseases. However, further researches on isolation and characterization of bioactive compounds along with pre-clinical trials are compulsory to figure out its pharmacological applications.

Mangifera indica Extracts as Novel PKM2 Inhibitors for Treatment of Triple Negative Breast Cancer.

Pyruvate kinase (PK), a key enzyme that determines glycolytic activity, has been known to support the metabolic phenotype of tumor cells, and specific pyruvate kinase isoform M2 (PKM2) has been reported to fulfill divergent biosynthetic and energetic requirements of cancerous cells. PKM2 is overexpressed in several cancer types and is an emerging drug target for cancer during recent years. Therefore, this study was carried out to identify PKM2 inhibitors from natural products for cancer treatment. Based on the objectives of this study, firstly, plant extract library was established. In order to purify protein for the establishment of enzymatic assay system, pET-28a-HmPKM2 plasmid was transformed to E. coli BL21 (DE3) cells for protein expression and purification. After the validation of enzymatic assay system, plant extract library was screened for the identification of inhibitors of PKM2 protein. Out of 51 plant extracts screened, four extracts Mangifera indica (leaf, seed, and bark) and Bombex ceiba bark extracts were found to be inhibitors of PKM2. In the current study, M. indica (leaf, seed, and bark) extracts were further evaluated dose dependently against PKM2. These extracts showed different degrees of concentration-dependent inhibition against PKM2 at 90-360 µg/ml concentrations. We have also investigated the anticancer potential of these extracts against MDA-MB231 cells and generated dose-response curves for the evaluation of IC50 values. M. indica (bark and seed) extracts significantly halted the growth of MDA-MB231 cells with IC50 values of 108 µg/ml and 33 µg/ml, respectively. Literature-based phytochemical analysis of M. indica was carried out, and M. indica-derived 94 compounds were docked against three binding sites of PKM2 for the identification of PKM2 inhibitors. The results of in silico based screening have unveiled various PKM2 modulators; however, further studies are recommended to validate their PKM2 inhibitory potential via in vitro biochemical assay. The results of this study provide novel findings for possible mechanism of action of M. indica (bark and seed) extracts against TNBC via PKM2 inhibition suggesting that M. indica might be of therapeutic interest for the treatment of TNBC.

Furanodiene: A Novel, Potent, and Multitarget Cancer-fighting Terpenoid.

Natural products have served as a limitless reservoir of bioactive scaffolds for drug discovery against several disorders. Furanodiene is a bioactive natural product isolated from several plants of genus Curcuma. Its therapeutic potential against cancer, inflammation, and angiogenesis has been well-documented. The current review is an update about the natural sources and anti-cancer action mechanism of furanodiene. Furanodiene exerts its anti-cancer effects via induction of apoptosis in several cancer types by modulating MAPKs/ERK, NF-κB, and Akt pathways. Furanodiene has been systematically studied for its anti-cancer potential. However, pharmacokinetics, pharmacodynamics, pre-clinical and clinical studies still needed to be conducted to completely validate the potential of furanodiene for the treatment of cancer.

The isolation of secondary metabolites from Rheum ribes L. and the synthesis of new semi-synthetic anthraquinones: Isolation, synthesis and biological activity.

Rheum ribes L. (Rhubarb) is one of the most important edible medicinal plants in the Eastern Anatolia region and is called "Iskin" by local people. Resveratrol and 6-O-methylalaternin were isolated from the Rhubarb for the first time in addition to well-known secondary metabolites including emodin, aloe-emodin, ß-sitosterol and rutin. The new semi-synthetic anthraquinone derivatives with the NαFmoc-l-Lys and ethynyl group were synthesized from the isolated anthraquinones emodin and aloe-emodin of Rhubarb to increase the bioactivities. Aloe-emodin derivative with NαFmoc-l-Lys shows the highest inhibition values by 94.11 ± 0.12 and 82.38 ± 0.00% against HT-29 and HeLa cell lines, respectively, at 25 µg/mL. Further, modification of the aloe-emodin with both the ethynyl and the NαFmoc-l-Lys groups showed an antioxidant activity-enhancing effect. From molecular docking studies, the relative binding energies of the emodin and aloe-emodin derivatives to human serum albumin ranged from -7.30 and -10.62 kcal/mol.

Caffeic acid derivatives (CAFDs) as inhibitors of SARS-CoV-2: CAFDs-based functional foods as a potential alternative approach to combat COVID-19.

BACKGROUND: SARS-CoV-2, an emerging strain of coronavirus, has affected millions of people from all the continents of world and received worldwide attention. This emerging health crisis calls for the urgent development of specific therapeutics against COVID-19 to potentially reduce the burden of this emerging pandemic. PURPOSE: This study aims to evaluate the anti-viral efficacy of natural bioactive entities against COVID-19 via molecular docking and molecular dynamics simulation. METHODS: A library of 27 caffeic-acid derivatives was screened against 5 proteins of SARS-CoV-2 by using Molegro Virtual Docker 7 to obtain the binding energies and interactions between compounds and SARS-CoV-2 proteins. ADME properties and toxicity profiles were investigated via www.swissadme.ch web tools and Toxtree respectively. Molecular dynamics simulation was performed to determine the stability of the lead-protein interactions. RESULTS: Our obtained results has uncovered khainaoside C, 6-O-Caffeoylarbutin, khainaoside B, khainaoside C and vitexfolin A as potent modulators of COVID-19 possessing more binding energies than nelfinavir against COVID-19 Mpro, Nsp15, SARS-CoV-2 spike S2 subunit, spike open state and closed state structure respectively. While Calceolarioside B was identified as pan inhibitor, showing strong molecular interactions with all proteins except SARS-CoV-2 spike glycoprotein closed state. The results are supported by 20 ns molecular dynamics simulations of the best complexes. CONCLUSION: This study will hopefully pave a way for development of phytonutrients-based antiviral therapeutic for treatment or prevention of COVID-19 and further studies are recommended to evaluate the antiviral effects of these phytochemicals against SARS-CoV-2 in in vitro and in vivo models.