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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.

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.

In this study, Centaurea sivasica Wageitz (Asteraceae) methanol extract was examined regarding phytochemical composition, in vitro antioxidant properties, ability to inhibit tyrosinase, α-amylase, α-glucosidase enzymes, and antimicrobial effects. Also, possible binding and interactions of phytochemicals with enzymes by molecular docking were determined. The extract's phenolic amount was 21.42 mg GAE/g extract, and the extract was determined to be rich in flavonoids (19.73 mg RE/g extract). Due to the results of liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) analysis, the main components of the methanol extract was scutellarin (27843.91 μg/g), quercimeritrin (3629.85 μg/g), chlorogenic acid (2519.68 μg/g) and baicalin (920.49 μg/g). The methanol extract was found to show remarkable activity in all antioxidant activity tests and had a high potential to inhibit the enzymes examined. The extract was radical scavenging on (DPPH and ABTS), reducing power (FRAP and CUPRAC), phosphomolybdenum assays were measured as 2.72, 69.58, 44.78, 141.18, 109.25 mg TE/g extract, respectively. Tyrosinase, α-amylase, and α-glucosidase inhibitory activities were 36.81 mg KE/g extract, 252.60 and 279.40 mg AKE/g extract, respectively. Scutellarin inhibited the tyrosinase enzyme very effectively, and its effect was found as 43.32 µM or 20.38 µg/mL. The extract showed different inhibition zones (16.3, 16.0, 15.0, 15.6 mm) and MIC values (500–1000 µg/mL) on the microorganisms examined (B. cereus, S. aureus, E. coli, C. albicans). In molecular docking studies, the most abundant scutellarin in the extract was shown to affect both tyrosinase and α-glucosidase inhibition significantly.

Inhibitors of xanthine oxidase (XO) are effective and most major therapeutic drugs for the management of gout. Chalcone compounds are important in terms of biological activity and have great importance in enzyme studies in recent years. In the presented study, the effects of some chalcones on the enzyme were tested in vitro by the spectrophotometric method. Compounds showed an inhibitory effect between 7.21±0.07 and 13.78±0.13 µM IC50 values. The conformations and interactions of the compounds in the active site of the enzyme were determined by the molecular docking method using Molegro Virtual Docker software. Molecular modeling studies show that the B ring of chalcones has a significant contribution to the inhibition effect on the XO enzyme. The presented study suggests that chalcones may be a potential inhibitory group for XO.

The composition of the essential oil obtained from the dried aerial parts of Senecio massaicus was analyzed by GC/MS. Twenty-two components have been identified and represented 97.41 % of the total oil composition. The major constituents of the essential oil were m-cymene (30.58 %), n-hexadecanoic acid (14.88 %) and docosane-11-decyl (10.43 %). Four methods were used to determine the antioxidant activity: DPPH, ABTS, CUPRAC and reducing power assay. The results indicate that the essential oil extract has moderate to low activity compared to the reference antioxidant compounds. In vitro anticholinesterase activity of the essential oil has also been studied. It exhibited higher inhibitory activity against butyrylcholinesterase (BChE) than against acetylcholinesterase (AChE). Docking studies conducted for Alzheimer's disease-related enzymes have displayed that compounds docosane-11-decyl and octaethyleneglycol monododecyl ether have strong potency, and compounds 15,15’Bi1,4,7,10,13-pentaoxacyclohexadecane and n-Hexadecanoic acid have moderate inhibitory potential. In addition, these three compounds (Docosane-11-decyl, octaethyleneglycol monododecyl ether and 15,15’Bi1,4,7,10,13-pentaoxacyclohexadecane) of the essential oil displayed strong interaction against SARS-CoV-2 main protease and Nsp15 endoribonuclease. Therefore, it could be useful to provide anticholinesterase agent and anti-coronavirus candidate drugs. © 2021 Har Krishan Bhalla & Sons.

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...

beta-Lactamases are enzymes that catalyze the hydrolysis of the beta-lactam ring, resulting in loss of function in beta-lactam antibiotics. In this report, the inhibition of beta-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 beta-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 K-i values of 27.65 +/- 4.22, 58.92 +/- 12.83 and 67.42 +/- 5.77 mu M, 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, Agri Ibrahim Cecen University Scientific Research Council [SHMYO.18.001], This work was supported by the Agri Ibrahim Cecen University Scientific Research Council under grant number SHMYO.18.001.

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

Enzyme assays are standardized experimental protocols, which are established in order to measure the activity or concentration of enzymes in biochemical or cell-based systems. Mostly enzymatic assays are based upon the detection of fluorescent, luminescent, or spectrophotometric endpoint signal. During recent years, florescence-based, absorbance-based, and luminescence-based high-throughput screening assays have been developed and widely used in various fields. Enzyme assays represent an important tool for screening of sample libraries in context of drug discovery. In addition, enzyme assays are valuable for diagnosis of several diseases in clinical settings due to their high sensitivity, specificity, and rapid response. In this chapter, we aim to provide an understanding of the working principle of enzymatic assays and their applications with some specific examples of enzyme assays that are used for drug discovery and diagnostic purpose.

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, thein vitroinhibitory effects of various compounds on commercially available recombinant human AR (rAR) enzyme activity were investigated. The IC(50)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 mu M, respectively. 6-Hydroxy flavone and syringic acid competitively inhibited rAR with respect to the NADPH with K(i)values 0.509 +/- 0.036 and 0.842 +/- 0.012 mu M. In addition, docking studies were performed to evaluate the potential enzyme binding positions of the compounds. Ourin vitroandin silicoresults indicated that the 6-hydroxy flavone may be a good lead compound in the development of AR inhibitors to prevent diabetic complications., Agri Ibrahim Cecen University Scientific Research [SYO.18.003], This study was financially supported by Agri Ibrahim Cecen University Scientific Research [Project number: SYO.18.003].

Objectives: Earthworms have a large impact on the soil ecosystem. They are quite sensitive to pollutants. Purification and biochemical characterization of glucose-6-phosphate dehydrogenases (G6PD) from the earthworm species Eisenia fetida were aimed. The determination of the toxicity potentials of some soil pollutants on G6PD activity was intended. Methods: G6PD was isolated using 2',5'-ADP-Sepharose 4B affinity column. Enzyme purity and molecular mass were determined by SDS-PAGE. Its biochemical properties investigated. The effects of some soil pollutants on the enzyme were studied in vitro. Results: Enzyme was purified with 28% yields and 232 fold. Optimum pH and buffer concentration, optimal and stable temperature was determined as pH: 8.5, 60 mM, 25 degrees C and 20 degrees C. Its molecular weight estimated as 36 kDa. The Ni2+, Hg2+, Pb2+, Cr2+, and Fe2+ ions with IC50 values in the range of 56 +/- 06-120 +/- 20 mu M and the diniconazole, metalaxyl, methomyl, carboxyl, and oxamyl with IC50 values in the range of 7.6 +/- 1.2-77 +/- 12 mu M exhibited an inhibitory effect on G6PD. Conclusions: G6PD was isolated and characterized from E. fetida. Its catalytic activity decreased with very low concentration by pesticides and metal ions. The results indicated that the inhibition of G6PD may be important in the toxicity mechanism of pollutants on this earthworm., Cankiri Karatekin University [FF200217B42], This research was supported by Cankiri Karatekin University (Project No: FF200217B42).

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 M

New Schiff bases were synthesized (Z)-4-((4-(diethylamino) benzylidene) amino)-N-(3,4-dimethylisoxazol-5-yl) benzenesulfonamide (L1) and (Z)-4-((4-(dimethylamino)benzylidene)amino)-N-(5-methylisoxazol-3-yl) benzenesulfonamide (L2) derived from sulfamethoxazole (S1)/sulfisoxazole (S2) and substituted salicylaldehyde. The synthesized compounds were characterized by FT-IR, H-1-C-13 NMR, LC-MS. We evaluated the effects of compounds on eight enzyme activities by spectrophotometric assays at final concentrations of 0.5-5 mu g. L1 acted as an inhibitor on cholesterol esterase, tyrosinase and alpha-amylase activities with IC50 values 38, 38 and 173 mu M. Tyrosinase, alpha-glucosidase, cholesterol esterase, and a-amylase enzymes were inhibited by L2 with IC50 values 24, 46, 63, and 231 mu M. To comprehend the binding interactions between the inhibitors and enzymes with low IC50 values, molecular docking studies of compounds were performed for cholesterol esterase and tyrosinase. Finally, molecular docking was performed to determine the probable binding mode of the designed compounds into the active site of enzymes. DFT calculations were carried out at the B3LYP levels of theory with 6-311G ++ (d, p) basis set for compounds. (C) 2019 Elsevier B.V. All rights reserved.

Carbonic anhydrases (CAs) play a significant function in diverse pathological and physiological processes. Their inhibitors and activators are suitable molecules to use as a drug in the treatment of different disease. In the present study, seven natural compounds, namely didymin, retusin isoquercitrin, silymarin, verbascoside, teucroside, and 3′-O-methylhypolaetin 7-O-[6′′′-O-acetyl-β-D-allopyranosyl-(1→2)]-6′′-O-acetyl-β-D-glucopyranoside were isolated from Mentha spicata, Sideritis libanotica linearis, Platanus orientalis, Teucrium chamaedrys subsp. chamaedrys, and Silybum marianum. The influences of compounds on the carbonic anhydrase I(hCAI) and II(hCAII) purified from human erythrocytes were tested. Five phenolic compounds acted as an inhibitor on the activity of hCAI, and IC50 values were computed between 18.16 and 172.5 μM. Isozyme hCAII is only inhibited by silymarin with an IC50 value of 43.12 μM. This isoenzyme was effectively activated by five natural compounds with AC50 values in the range of 2.98–18.53 μM. To understand the binding patterns of molecules that show activation effect against hCAII, molecular docking was done using Leadit 2.3.2 software, and calculated between −19.05 and −14.42 (kJ/mol) binding energies. Both in vitro and in silico results demonstrated that the best activators against hCAII were teucroside and isoquercitrin, with AC50 values of 2.98 and 3.17 μM, and binding energies −19.05 and −18.01 (kJ/mol), respectively. According to the ADME results, retusin demonstrated physicochemical and pharmacokinetic properties specific to the drug candidates.

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

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.

Natural products have emerged as a treasure trove of novel chemical scaffolds for drug discovery against various diseases including inflammation, cardiovascular diseases, osteoporosis, and cancer. Isoflavones, polyphenolic compounds, from plants belonging to the Fabaceae family act as phytoestrogens and possess a pseudo-hormonal effect by binding with estrogen receptors in the human body. Due to this property, isoflavones exhibit multiple health-promoting benefits. In the class of isoflavones, biochanin A and biochanin B (formononetin) are prominent compounds renowned for their wide therapeutic window against numerous pathological conditions. Biochanin A and B possess antidiabetic, antiobesity, hepatoprotective, anticancer, and antiinflammatory activities. Biochanin A and B are rapidly absorbed in the body and possess safe pharmacokinetics as indicated by several in vivo investigations. This chapter aims to elaborate on the natural sources, pharmacological potential as well as bioavailability and pharmacokinetics of biochanin A and B, suggesting these compounds as interesting and safe candidates for drug design and development in the near future.

Herein we present the synthesis, and biological evaluation of new Schiffbases incorporating (2-hydroxy-5-methylbenzaldehyde sulfisoxazole (S2M-S1) and 2-hydroxy-5-methylbenzaldehyde sulfamethoxazole (S1M-S1) derived from sulfisoxazole (S2)/sulfamethoxazole (S1) and substituted salicylaldehyde and their Pd (II), Cu(II) complexes. The synthesized compounds were characterized by FT-IR, H-1-C-13 NMR, LC-MS, magnetic susceptibility and conductivity measurements. The molecular structure of S2M-S1 was also determined by the single crystal X-ray diffraction technique and was found to crystallize in the monoclinic, space group P1 21/n 1. We investigated the effects of molecules on human carbonic anhydrase isoenzyme II (hCAII). Cu(S2M-S1)(2), Pb(S2M-S1)(2), Pb(S1M-S1)(2), and Cu(S1M-S1)(2), exhibited inhibitory effects with 10, 20, 42 and 67 mu M IC50 value, respectively. Also, molecular Docking studies performed and anticancer activities of newly synthesized compounds were evaluated against three human cancer cell lines with the sulfonamide B test. S2M-S1, S1M-S1 compounds and their Cu (II) complexes exhibited promising cytotoxic activity against all cell lines. IC50 values for breast (MCF7) cells are 40 mu M for S2M-S1, S1M-S1 compounds and their Cu (II) complexes. (C) 2020 Elsevier B.V. All rights reserved.

Cancer is a multifaceted disease characterized by deregulated epigenetic, genetic and metabolic signals which affect cellular metabolism and apoptosis. Breast cancer is regarded to be the most common malignancy in the women worldwide. The side effects of chemo-drugs such as non-selectivity, toxicity and resistance urge scientists to find more potent and safer drugs. Natural products from plants provide an extensive array of chemical scaffolds with biosafety profiles, and safer health effects. Curcuma, a genus of family Zingiberaceae, comprises of about 110 species natively distributed as well as cultivated in South Asia, China, Australia, Sri Lanka, West Indies, and Peru. This plant is used as a remarkable pharmacological remedy to prevent and cure various pathological disorders including cancer. The chemical constituents of this plant, terpenoids and betaketones, specifically act as the anti-breast cancer agents. Curcuma, the marvel of nature, can be regarded as panacea due to its versatile molecular targets and spacious therapeutic window. Various investigations on the essential oils and dry rhizome conclude that the chemical constituents of this plant e.g., curcumin, germacrone, furanodienone, bisdethoxycurcumin, demethoxycurcumin, curcumol, and aromatic turmerone are responsible for its anti-breast cancer potential. These compounds, either as single compound or in combinations with other drugs, are known to arrest cell cycle and induce apoptosis in breast cancer cells by modulating various signaling cascades including NF-κB, STAT3, PI3k/Akt/mTOR and MAPK. This book chapter intends to comprehend the biological and pharmacological mode of action of Curcuma-derived anti-breast cancer compounds in order to update the researchers and scientific community about the pharmaceutical potential of plants belonging to this genus.

Nature as an infinite treasure of chemotypes and pharmacophores will continue to play an imperative role in the drug discovery. Natural products (NPs) such as plant and fungal metabolites have emerged as leads in drug discovery during recent years due to their efficacy, safety and selectivity. The current review summarizes natural sources as well as pharmacological potential of hispolon which is a major constituent of traditional medicinal mushroom Phellinus linteus. The study aims to update the scientific community about recent developments of hispolon in the arena of natural drugs by providing insights into its present status in therapeutic pursuits. Hispolon, a polyphenol has been reported to possess anticancer, antidiabetic, antioxidant, antiviral and anti-inflammatory activities. It fights against cancer via induction of apoptosis, halt in cell cycle and inhibition of metastasis by targeting various cellular signaling pathways including PI3K/Akt, MAPK and NF-κB. The current review proposes that hispolon provides a novel opportunity for pharmacological applications and its styrylpyrone carbon skeleton might serve as an attractive scaffold for drug development. However, future researchers are recommended to assess bioavailability, toxicological limits, pharmacokinetic and pharmacodynamic profiles of hispolon, in order to establish its potential as a potent multi-targeted drug in the near future., Graphical abstract Image 1

Natural products, being richly endowed with curative powers, have become spotlight for biomedical and pharmaceutical research to develop novel therapeutics during recent years. Ginkgetin (GK), a natural non-toxic biflavone, has been shown to exhibit anti-cancer, anti-inflammatory, anti-microbial, anti-adipogenic, and neuroprotective activities. GK combats cancer progression by arresting cell cycle, inducing apoptosis, stimulating autophagy, and targeting many deregulated signaling pathways such as JAK/STAT and MAPKs. GKhalts inflammation mediators like interleukins, iNOS, COX-2, PGE2, NF-κB, and acts as an inhibitor of PLA2. GK shows strong neuroprotection against oxidative stress-promoted cell death, inhibits cerebral micro-hemorrhage, decreases neurologic deficits, and halts apoptosis of neurons. GK also acts as anti-fungal, anti-viral, anti-bacterial, leishmanicidal and anti-plasmodial agent. GK shows substantial preventive or therapeutic effects in in vivo models of many diseases including atherosclerosis, cancer, neurodegenerative, hepatic, influenza, and inflammatory diseases. Based on various computational, in vitro and in vivo evidences, this article demonstrates the potential of ginkgetin for development of therapeutics against various diseases. Although GK has been systematically studied from pharmacological point of view, a vast field of pharmacokinetics, pre-clinical and clinical studies is still open for the researchers to fully validate its potential for the treatment of various diseases.

Natural products, an infinite reserve of bioactive molecules, will continue to serve humans as an important source of therapeutic agents. Germacrone is a bioactive natural compound found in the traditional medicinal plants of family Zingiberaceae. This multifaceted chemical entity has become a point of focus during recent years due to its numerous pharmacological applications, e.g., anticancer, anti-inflammatory, antiviral, antioxidant, anti-adipogenic, anti-androgenic, antimicrobial, insecticidal, and neuroprotective. Germacrone is an effective inducer of cell cycle arrest and apoptosis in various cancers (breast, brain, liver, skin, prostate, gastric, and esophageal) via modulation of different cell signaling molecules and pathways involved in cancer proliferation. This is the first report highlighting the wide spectrum of pharmacological activities exhibited by germacrone. The reported data collected from various shreds of evidences recommend that this multifaceted compound could serve as a potential drug candidate in the near future.

A series of novel Norcantharimide derivatives were synthesized and their structures were characterized by FTIR, 1H and 13C NMR spectroscopy as well as elemental analyses. The absorption, distribution, metabolism and excretion (ADME) properties of the synthesized molecules were investigated. The results obtained in silico demonstrated that these molecules can be considered as orally active drug candidates due to their physicochemical properties. Also, docking studies demonstrated that all derivatives exhibit a good theoretical affinity with MolDock Score in between 124–138 against the main protease of Coronavirus Disease 2019 (COVID‐19 Mpr°) that caused worldwide epidemics. We believe that newly synthesized norcantharimide derivatives can guide many future studies in organic synthesis, medicine and pharmaceutical applications., A series of new novel Norcantharimides have been synthesized and their absorption, distribution, metabolism and excretion (ADME) properties were investigated. The results obtained in silico showed that these molecules can be considered orally active drug candidates, taking into account their physicochemical properties. In addition, placement studies have shown that all derivatives exhibit good theoretical affinity with the 124–138 MolDock Score against the main protease of Coronavirus Disease 2019 (COVID‐19 Mpr°), which causes worldwide outbreaks.

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 coronavirus COVID-19 epidemic has wreaked havoc on inhabitants of earth killing thousands of humans from more than 150 countries. The epidemic has put a number of countries under complete lockdown and the deadly situation is still prevailing around the globe. Vaccines have been long known as the most effective means of preventing viral infections. However, the lack of vaccines against COVID-19 has further worsened the situation. In this time of health crisis, it is the duty of scientific research community to provide alternative, effective and affordable strategies to vaccinate human bodies against viral infections-COVID-19 based on focused experimental approaches. Growing evidence suggests that certain natural foods and lifestyle changes have potential to optimize immune functions against viral infections including improving defense function, resistance towards invading pathogens, while maintaining self-tolerance. Boosting immune system gives an edge in fending off viruses and staying healthy. This review presents the six smart steps to add to your to-do list which let the inner work of immunity take place against viral infections-COVID-19 by dissolving the powers of disease and illness. Many of these factors are associated in their functions to improve or properly maintain the immune function such as promoting anti-inflammatory functions, inhibiting pro-inflammatory mediators, modulating cell-mediated immunity, altering the antigen-presenting cellular functions as well as promoting communication between the innate and adaptive immune responses. Thus, a scientific illustration of boosting the immune system by proper sleep, moderate exercise, avoiding stress, utilizing vitamins enriched foods, intake of more water and use of fruits and vegetables will hopefully help the community to deal with the coronavirus by vaccinating the human systems naturally.

COVID-19, a rapidly spreading new strain of coronavirus, has affected more than 150 countries and received worldwide attention. The lack of efficacious drugs or vaccines against SARS-CoV-2 has further worsened the situation. Thus, there is an urgent need to boost up research for the development of effective therapeutics and affordable diagnostic against COVID-19. The crystallized form of SARS-CoV-2 main protease (Mpro) was demonstrated by a Chinese researcher Liu et al. (2020) which is a novel therapeutic drug target. This study was conducted to evaluate the efficacy of medicinal plant-based bioactive compounds against COVID-19 Mpro by molecular docking study. Molecular docking investigations were performed by using Molegro Virtual Docker 7 to analyze the inhibition probability of these compounds against COVID-19. COVID-19 Mpro was docked with 80 flavonoid compounds and the binding energies were obtained from the docking of (PDB ID: 6LU7: Resolution 2.16 Å) with the native ligand. According to obtained results, hesperidin, rutin, diosmin, apiin, diacetylcurcumin, (E)-1-(2-Hydroxy-4-methoxyphenyl)-3-[3-[(E)-3-(2-hydroxy-4- methoxyphenyl)-3-oxoprop-1-enyl]phenyl]prop-2-en-1-one, and beta,beta'-(4-Methoxy-1,3- phenylene)bis(2'-hydroxy-4',6'-dimethoxyacrylophenone have been found as more effective on COVID-19 than nelfinavir. So, this study will pave a way for doing advanced experimental research to evaluate the real medicinal potential of these compounds to cure COVID-19.

Nature has provided prodigious reservoirs of pharmacologically active compounds for drug development since times. Physcion and physcion 8-O-β-D-glucopyranoside (PG) are bioactive natural anthraquinones which exert anti-inflammatory and anticancer properties with minimum or no adverse effects. Moreover, physcion also exhibits anti-microbial and hepatoprotective properties, while PG is known to have anti-sepsis as well as ameliorative activities against dementia. This review aims to highlight the natural sources and anticancer activities of physcion and PG, along with associated mechanisms of actions. On the basis of the literature, physcion and PG regulate multitudinous cell signaling pathways through the modulation of various regulators of cell cycle, protein kinases, microRNAs, transcriptional factors, and apoptosis linked proteins resulting in the effective killing of cancerous cells in vitro as well as in vivo. Both compounds effectively suppress metastasis, furthermore, physcion acts as an inhibitor of 6PGD and also plays an important role in chemosensitization. This review article suggests that physcion and PG are potent anticancer drug candidates, but further investigations on their mechanism of action and pre-clinical trials are mandatory in order to comprehend the full potential of these natural cancer killers in anticancer remedies.

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

The fluorinated chalcones were synthesized by Claisen-Schmidt condensation between 4′-morpholineacetophenone and various fluorinated benzaldehydes in the presence of NaOH in methanol. The synthesized compounds [1–7] were evaluated their antiproliferative activity against HeLa and C6 cell lines. Among them, compounds 4 and 5 were determined to have anticancer activity against HeLa cells line (IC 50 values of 7.74 and 6.10 μg/mL, respectively). The anticancer activity results were shown that compounds 3 , and 6 had inhibitory against C6 cells (IC 50 values of 12.80 and 4.16 μg/mL, respectively). The compounds 1 and 2 had high antiproliferative activity with non-cytotoxicity. All of the new compounds, except for compound 4 showed inhibition against the human isozyme hCA I with IC 50 in the range of 0.5–1,16 mM. Pyruvate kinase M2 (PKM2) was effectively inhibited by compound 4 with IC 50 = 26 μM.

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., Graphical Abstract Image, graphical abstract

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, β-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.

Iron is an indispensable element for vital activities in almost all living organisms. It is also a cofactor for many proteins, enzymes, and other essential complex biochemical processes. Therefore, iron trafficking is firmly regulated by Hepcidin (Hamp), which is regarded as the marker for iron accumulation. The disruption of iron homeostasis leads to oxidative stress that causes various human diseases, but this mechanism is still unclear. The aim of this study is to provide a better in vivo and in vitro understanding of how long-term iron overload affects the gene expression and activities of some antioxidant enzymes, such as glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and glutathione reductase (GR) in the spleen. The findings of this study show that iron overload reduces the gene expression of G6pd, 6pgd, and Gr, but its actual effect was on the protein level. © 2018 Wiley Periodicals, Inc. PRJ2010/277, PRJ2015/97 Conceived and designed the experiments: HB (group leader) and SA. Performed the experiments: HB, NG, CG, HC, SNC, SA, and EFK. Analyzed the data: HB, NG, CG, EFK, and OE. Contributed reagents/ materials/analysis tools: HB, SA, and OE. Wrote the paper: HC and HB. This study has been supported by Ataturk University Scientific Research Projects Coordination Commission (ATAUNI?BAP) with project number PRJ2010/277 and PRJ2015/97.

New Schiff bases (E)-N-(3,4-dimethylisoxazol-5-yl)-4-(2-hydroxy-3-methoxybenzylidene) amino) benzenesulfonamide (LI), (E)-N-(3,4-d imethylisoxazol-5-yl)-4-(2-hydroxy-4-methoxybenzylidene) amino)benzenesulfonamide (L2) and (E)-4-((4-methoxy-2-hydroxybenzylidene)amino)-N-(5-methylisoxazol-3-yl)benzene sulfonamide (L3) derived from sulfamethoxazole (S1)/sulfisoxazole (S2) and substituted salicylaldehydes and their Pd (II), Cu (II) complexes were synthesized for the first time. The synthesized compounds were characterized by FT-IR, H-1-C-13 NMR, LC-MS, magnetic susceptibility, conductivity measurements and thermal analysis (TGA). The complexes having general composition of [ML2] were found. The results of elemental analysis showed 1:2 (metal/ligand) stochiometry for all the complexes. Magnetic and spectral data indicate a square planar geometry for Pd (II) complexes and a distorted tetrahedral geometry for Cu (II) complexes. H-1 and C-13 shielding tensors for crystal structure were calculated with GIAO/DFT/B3LYP/6-311++G(d,p) methods in CDCl3. The nonlinear optical (NLO) properties and frontier molecular orbitals have been investigated by B3LYP/6-311++G(d,p) and B3LYP/LanL2DZ level of theory. The ligands and their metal chelates have been screened for their antimicrobial activities using the microdilution method (as MICs) method against the selected Staphylococcus aureus, Eschericha coli, Klebsiella pneumonia and Stenotrophomonas Maltophilia. The inhibition activities of these compounds on carbonic anhydrase II (CA II) and carbonic anhydrase I (CAI) have been investigated by comparing IC50 values, and it has been observed that Cu (II) complex (IC50 values = 6-22 mu M range) and Pd(II) (IC50 values = 16-138 mu M range) have had very high inhibition potencies on enzymes than ligands (not inhibition for CAI, IC50 values =173-346 mu M range). (C) 2018 Elsevier B.V. All rights reserved.

G6PD, 6PGD and GR have been purified separately in the single step from rat lung using 2', 5'-ADP Sepharose 4B affinity chromatography. The purified enzymes showed a single band on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The molecular weights of the enzymes were estimated to be 134 kDa for G6PD, 107 kDa for 6PGD and 121 kDa for GR by Sephadex G-150 gel filtration chromatography, and the subunit molecular weights was respectively found to be 66, 52 and 63 kDa by SDS-PAGE. Optimum pH, stable pH, optimum ionic strength, optimum temperature, KM and Vmax values for substrates were determined. Product inhibition studies were also performed. The enzymes were inhibited by levofloxacin, furosemide, ceftazidime, cefuroxime and gentamicin as in vitro with IC50 values in the range of 0.07-30.13 mM. In vivo studies demonstrated that lung GR was inhibited by furosemide and lung 6PGD was inhibited by levofloxacin.

Pyruvate kinase isoenzyme M2 (PKM2) is expressed excessively in many different cancer types and it plays an important role in the control of glucose metabolism. Thus, it is evaluated as an important target in the development of medication for cancer. The flavonoids comprise a large group of natural products with variable phenolic structures and occur mainly in plants. They are of great interest due to their biological properties. In this study, the effects of various flavonoid derivatives on the PKM2 enzyme activity were analyzed in vitro. The flavonoid derivatives 1 and 2 showed inhibition effect with IC50 values of

It is well known that cancer cells have an altered metabolism both to meet the energy needs and to provide initial molecules for the synthesis of macromolecules. To cope with the new metabolic state, different forms of certain enzymes are expressed in extreme amounts. These enzymes are seen as very attractive targets to deal with cancer. Pyruvate kinases isoenzyme M2 (PKM2) is a key enzyme that determines whether glucose is used for energy or synthesis of biosynthetic molecules. The dimeric form of PKM2 main form in several cancer cells serves the formation of synthetic precursors required for the cell growth and proliferation from glycolytic intermediates.This article reviews appropriate publications on PKM2 activators from the points of view of synthesis and biological activities between 2011-2017. Herein, based on the chemical structure, PKM2 activators are classified into sulfonamide, phenolic, carboxamide and pyridopyrimidinone derivatives.PKM2 activation inhibits cell growth and proliferation by decreasing a number of biomolecules required for cell building. Therefore; PKM2 activators are considered as an ideal drug for or the treatment of many cancer pathogens. It is necessary to discover new, more active and selective compounds for PKM2 activation.

Dihydrofolate reductase (DHFR) plays a fundamental role in cellular metabolism and cell growth. Inhibition of this enzyme will cause a decrease in the amount of folate that occurs in many metabolic processes, and the deficiency of which may cause various diseases. This study investigated the effects of some drugs and phenolic compounds on DHFR activity in vitro. To determine the inhibitory effect of compounds, enzyme activity was measured with a final concentration of an inhibitor ranging from 10 μM to 51 mM. DHFR was inhibited effectively by naringin, ferulic acid, and levofloxacin with IC50 values under 660 μM. Syringic acid, cefepime, ceftizoxime, cefazolin, ceftriaxone, and ceftazidime exhibited inhibitory effects on the enzyme activity with IC50 values in the range of 3.840-30.224 mM. K(i) constants were calculated using the Cheng-Prusoff equation. K(i) constants calculated in the range of 0.009-2.024 mM with respect to nicotinamide adenine dinucleotide phosphate oxidase (NADPH) and in the range of 0.060-5.830 mM about FH2.

PKM2 is an important target for designing anticancer drug. Inhibitors and activators of this enzyme are suitable molecules for use in treating cancer. The aim of the present study was to investigate the effect of certain flavones on PKM2. Apigenin, wogonin, flavone, 3-hydroxyflavone, 5-hydroxyflavone, 6-hydroxyflavone, and 7-hydroxyflavone effectively inhibited PKM2, with IC50 in the range of 0.99-2.120 μM. The kinetic study indicated that these compounds acted as noncompetitive with Ki values of 3.53-5.67 μM toward phosphoenolpyruvate. Scutellarin and tangeritin demonstrated strong activation effect with AC50 values < 2 μM. Diosmetin, baicalin, baicalein, and luteolin showed an intermediate-level activator effect. These results demonstrate that flavone and their analogs could serve as leading compounds to develop new potent and selective inhibitor and activator for PKM2.

Polyphenols are the important compounds that have various bioactivities. They constitute vital active agents of not only daily diet but also natural medicines that are used traditionally. It is generally considered that they are safe because they are natural. In some conducted studies, different negative effects of these compounds were mentioned. Twelve phenolic compounds have been assayed to determine the effect of inhibition on glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD) enzymes activity. For in vitro studies, the enzymes were purified from human erythrocytes using 2',5'-ADP Sepharose 4B affinity chromatography. Naringenin, caffeic acid, ellagic acid, ferulic acid, and sinapic acid against two enzymes, hesperidin and polydatin, only on G6PD activity and chrysin solely against 6PGD showed inhibitory effect. Chlorogenic acid, p-coumaric acid, and syringic acid did not exhibit an effect on the activity of the two enzymes.

The present study was aimed to investigate characterization and purification of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and glutathione reductase from rat heart and the inhibitory effect of three drugs. The purification of the enzymes was performed using 2',5'-ADP sepharose 4B affinity material. The subunit and the natural molecular weights were analyzed by SDS-PAGE and gel filtration. Biochemical characteristics such as the optimum temperature, pH, stable pH, and salt concentration were examined for each enzyme. Types of product inhibition and Ki values with Km and Vmax values of the substrates and coenzymes were determined. According to the obtained Ki and IC50 values, furosemide, digoxin, and dopamine showed inhibitory effect on the enzyme activities at low millimolar concentrations in vitro conditions. Dopamine inhibited the activity of these enzymes as competitive, whereas furosemide and digoxin inhibited the activity of the enzyme as noncompetitive.

Lipase is an enzyme having a lot of different industrial applications such as biodiesel production, biopolymer synthesis, enantiopure pharmaceutical productions, agrochemicals, etc. Its immobilized form on different substances is more conventional and useful than its free form. Supporting material was prepared using PVDF-co-HFP in laboratory conditions and attached 1,4-diaminobutane (DA) and epichlorohydrin (EPI) ligands to the membrane to immobilize lipase enzyme. The immobilization conditions such as enzyme amount, pH, the concentration of salt, thermal stability and activity were stabilized for our experimental setup. Then, biochemical characterizations were performed on immobilized lipase PVDF-co-HFP regarding optimal pH activity, temperature and thermal stability. Also, the desorption ratios of immobilized enzyme in two different pathway were investigated to confirm immobilization stability for 24 hours.

6-phosphogluconate dehydrogenase is an enzyme in the pentose phosphate path. The main functions of the pathway are the manufacture of the reduced coenzyme NADPH and the formation of ribose 5-phosphate for nucleic acid synthesis and nucleotide. Both NADPH and ribose 5-phosphate involve a critical biochemical process. Metals have been recognized as important toxic agents for living for a long time. It has been considered that they lead to in the emergence of many diseases. To evaluate whether metals is effect towards rat liver 6PGD, we apply various concentrations of metals and enzyme inhibition was analyzed using enzyme activity assays. The IC50 values of Pb+2, Cr+3, Co+2, Ni+2, Cd+2, and Va+2, metals on rat liver 6PGD were calculated as 138,138, 169, 214, 280, and 350 µM, respectively.