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Background: Plants are a main source of drugs for the therapy of a large number of diseases. Objective: The aim of the present work is to evaluate the in vitro antioxidant and anti-α-amylase and anti-peroxidases (HPR) potentials of phenolic extracts obtained from three spontaneous plants; growing in the South of Algeria such as (Chamomilla pubescens, Pulicaria crispa, and Rhanterium adpressum). This is the first report on the study of α-amylase and horseradish peroxidase (HRP) inhibitory activity for phenolic extracts from the Chamomilla pubescens and Pulicaria crispa plants. Method: The antioxidant activity was evaluated in vitro using four tests: DPPH, CUPRAC, FRAP, and ABTS. The phenolic, flavonoid, and tannin compounds of the three selected Algerian plants were quantified. Also, the inhibition of α-amylase and HRP was evaluated. Results: The quantification of the total phenolic contents revealed that they are widely variable, and depending on extraction solvents, the highest content was recorded by the ethyl acetate extract of Chamomilla pubescens (flowers) 774.93±60.14mg/100 g of dry matter. In all the antioxidant tests, ethyl acetate extracts showed the most effective activity, which the best was (VCEAC = 65.62 ±0.50 µM/g dry matter) of Pulicaria crispa for the DPPH test. Furthermore, the results of α-amylase and peroxidase inhibitory effects indicated that all plants extracts have inhibitory effects on the two enzymes, with AEIC values ranged from 76.55±3.54 to 149.54±6.68 μM/g of dry matter for the α-amylase, and CEIC values ranged from 8.89±2.22 to 9668.31±254.42 μM/g of dry matter for the peroxidase (HRP). Conclusion: The present study results suggest that the three Algerian spontaneous plant species (Rhanterium adpressum, Pulicaria crispa, and Chamomilla pubescens) inhibit peroxidase and α-amylase and exhibit a high antioxidant activity what can be related to the treatment of diabetes and thyroid diseases.

Over the past few years great progress has been achieved in anticancer therapy, but development of resistance and unavoidable side effects have incapacitated these fulfilments. Keeping in view this demanding condition, numerous drugs with unique antitumor mechanisms are under investigations including antimicrobials which have been shown to possess anti-inflammatory, immunomodulatory and cytotoxic effects. In this regard, both conventional and novel antimicrobials are being studied to explore their anticancer potential along with underlying mechanisms which may render them as effective anticancer drugs in near future. Moreover, the new approach of drug repurposing is also being encouraged especially in cancers in order to reduce cost and limit adverse effects. In recent times a cumulative number of studies have laid stress upon the antitumor properties of antimicrobials. Consequently, this study has been conducted to see comparative inhibitory effect of Sorafenib and its combination with a macrolide antibiotic Azithromycin on growth rate HepG2 cell line.

Plant-derived molecules have enduring usefulness in treating diseases, and herbal drugs have emerged as a vital component of global therapeutic demand. Angelica archangelica L. (A. archangelica), commonly known as garden angelica, is an aromatic food plant used in culinary procedures as a flavoring agent. In the traditional medicine system, it is regarded as an "Angel plant" due to its miraculous curative power. This review aims to provide a comprehensive summary of the plant's taxonomic profile, ethnopharmacology, Phytochemistry, and pharmacological activities. Various in vivo and in vitro experiments have validated that the plant possesses broad pharmacological potential. The biological activities attributed to the plant include anti-anxiety activity, anti-convulsant activity, cognition enhancer, antiviral activity, cholinesterase inhibitory potential, antiinflammatory activity, gastroprotective activity, and radioprotective activity. The beneficial effects of the plant are credited to its bioactive components, that is, coumarins and volatile oils. The review summarizes the pharmacological activities of crude extract and its bioactive fractions and has also explored their target-oriented effects. This review will be of value in undertaking further investigations on the plant with regard to exploring mechanism-based pharmacological approaches on A. archangelica.

Introduction: Murraya koenigii (L.) and Ficus carica L. are traditionally used plants with significant medicinal and nutritional values. Aim and Objective: The present study was focused on the evaluation of hydro-alcoholic and aqueous extracts of M. koenigii (L.) leaves [MKHA (M. koenigii (L.) hydro-alcoholic extract) and MKAQ (M. koenigii (L.) aqueous extract)] and dried fruits of F. carica L. [FCHA (F. carica L. hydro-alcoholic extract) and FCAQ (F. carica L. aqueous extract)] in the attenuation of markers of microvascular complications associated with diabetes mellitus which can be further used to investigate the pharmacological activity of these plants in treatment of diabetes and its complications. Material and Method: The attenuating effect of the extracts was evaluated by calculating the ALR1 enzyme inhibition in a kidney of Wistar rat, anti-glycation activity in bovine serum albumin (BSA) and erythrocyte sorbitol accumulation inhibition in heparinized human blood. Results: A significant inhibitory effect (IC50 6.47μg/ml,7.26μg/ml,8.93 μg/ml and 9.66μg/ml) was observed with different concentrations of extracts (MKHA, MKAQ, FCHA and FCAQ) respectively, against ALR enzyme. After the 4th week of incubation, the inhibition of AGEs formation by MKHA, MKAQ, FCHA and FCAQ (500μg/ml) was found to be 82.58%, 78.58%, 74.39% and 69.56% respectively. MKHA, MKAQ, FCHA and FCAQ were found to exhibit significant inhibition against the accumulation of sorbitol in RBCs with IC50 188.88 μg/ml, 247.74μg/ml, 291.94μg/ml and 345.34μg/ml, respectively. Conclusion: The administration of different concentrations of MKHA, MKAQ, FCHA and FCAQ significantly attenuated ALR, AGEs and sorbitol accumulation; hence, it can provide a basis for identification and development of new inhibitors of these biomarkers.

The global high prevalence of diabetes mellitus has resulted into the development of several oral hypoglycemic agents. However, these drugs have limited efficacy and harmful side effects, which call for the search for alternatives from natural sources. The inhibition of dipeptidyl peptidase‐4 (DPP‐4) activity increases the level of glucagon‐like peptide‐1 and glucose‐dependent insulinotropic polypeptide, which in turn reduces hyperglycemia by activating insulin secretion and inhibiting glucagon secretion. Some studies have reported the in vitro DPP‐4 inhibitory potential of functional foods, but there is no repository of information on these reports. This article is an attempt to present in concise form, reports of functional foods with DPP‐4 inhibitory potentials in vitro. This will guide the use of these foods as well as in antidiabetic drug development.

N-Aryl-3,4-dihydroisoquinoline carbothioamide analogues 1-22 were synthesized by a simple one-step reaction protocol and subjected to in vitro urease inhibition studies for the first time. All compounds 1-22 were found active and showed significant to moderate urease inhibitory potential. Specifically, analogues 1, 2, 4, and 7 were identified to be more potent (IC50 = 11.2 ± 0.81-20.4 ± 0.22 μM) than the standard thiourea (IC50 = 21.7 ± 0.34 μM). The structure-activity relationship showed that compounds bearing electron-donating groups showed superior activity. Molecular docking study on the most active derivatives revealed a good protein-ligand interaction profile against the corresponding target with key interactions, including hydrogen bonding, hydrophobic, and π-anion interactions.

The aim of this work was to synthesise derivatives from identified plant based pyridoindole lead scaffold, and to assess phosphodiesterase 5A inhibitory potential by in silico and in vivo. Pyridoin...

In this laboratory study, insecticidal and inhibitory potential of two chitin synthesis inhibitors (CSIs) viz. Buprofezin and Lufenuron were evaluated against okra shoot and fruit borer (OSFB). CSIs were applied on three days old larvae through different bioassay methods like topical or direct, okra-dip or indirect and combined (topical + leaf-dip). Data were collected on larval mortality, weight reduction and deformations of larvae and adults. Results showed that larval mortality and weight reduction were clearly dose, application methods and time dependent. In case of both CSIs, the highest mortality was found @ 1.0 ml/L that was followed by 0.75 ml and 0.50 ml/L respectively. Likewise, the highest body weight reduction was also found from 1.0 ml/L. In both cases, the concentration 0.5 ml/L was found less effective. In case of application methods, combined bioassay method was found superior than that of rest of the two methods. Moreover, a significant percentage of deformed larvae and adults were developed when 3 days old larvae were treated with either Buprofezin or Lufenuron @ 1.0 ml/L through combined bioassay method. The concentration 0.5 ml/L had very less efficacy on the development of deformed larvae or adults. Therefore, based on the laboratory findings Buprofezin and Lufenuron may be the potential component in IPM programmed, rather than their individual application, for controlling okra shoot and fruit borer as well as production of safe okra.

In search of potent urease inhibitor indole analogues (1–22) were synthesized and evaluated for their urease inhibitory potential. All analogues (1–22) showed a variable degree of inhibitory interaction potential having IC50 value ranging between 0.60 ± 0.05 to 30.90 ± 0.90 µM when compared with standard thiourea having IC50 value 21.86 ± 0.90 µM. Among the synthesized analogues, the compounds 1, 2, 3, 5, 6, 8, 12, 14, 18, 20 and 22 having IC50 value 3.10 ± 0.10, 1.20 ± 0.10, 4.60 ± 0.10, 0.60 ± 0.05, 5.30 ± 0.20, 2.50 ± 0.10, 7.50 ± 0.20, 3.90 ± 0.10, 3.90 ± 0.10, 2.30 ± 0.05 and 0.90 ± 0.05 µM respectively were found many fold better than the standard thiourea. All other analogues showed better urease interaction inhibition. Structure activity relationship (SAR) has been established for all analogues containing different substituents on the phenyl ring. To understand the binding interaction of most active analogues with enzyme active site docking study were performed. Communicated by Ramaswamy H. Sarma

A hipertensao arterial e o principal fator de risco para doencas cerebrovasculares e doencas isquemicas do coracao, sendo uma das causas mais importante para a morbidade e a mortalidade cardiovascular. Devido as limitacoes e severos efeitos colaterais dos farmacos disponiveis no mercado empregados para hipertensao, torna-se necessario o desenvolvimento de novos farmacos, mais eficazes e com menos eventos adversos. Assim, o objetivo deste estudo foi avaliar, por meio de tecnicas de modelagem molecular, a solubilidade em agua e o coeficiente de particao de nove compostos naturais inibidores da enzima conversora de angiotensina, alem de verificar os aspectos moleculas dessas interacoes. Foi observado que todos os compostos alvos do estudo possuem solubilidade adequada para interagir com barreiras biologicas hidrofobicas e fluidos hidrofilicos. Foi observado tambem, que os compostos naturais interagiram de forma atrativa com os aminoacidos do sitio ativo da enzima e com o ion zinco, fator de extrema importância para uma boa inibicao da enzima conversora de angiotensina. O presente estudo proporciona uma melhor compreensao da inibicao da enzima conversora de angiotensina por compostos naturais, o que pode contribuir para o desenvolvimento de novos anti-hipertensivos.

Aims: To evaluate the inhibitory activity of Lobeline natural alkaloid against dipeptidyl peptidase IV (DPP IV) enzyme by in silico and in vivo experiments. Study Design: Evaluation of Antidiabetic Activity of Lobeline alkaloid. Place and Duration of Study: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Aleppo University, Aleppo, Syria, between March 2020 and December 2020. Methodology: in silico study was carried out using iGEM docking software to predict the binding affinity of lobeline with DPP IV enzyme in comparison with the reference synthetic compound Sitagliptin. Then in vivo experiment was performed on HFD/alloxan induced diabetic mice to evaluate the anti hyperglycemic effect of lobeline. After treatment duration of 21 days, FBG and the inhibitory effect on DPP IV enzyme activity were measured. Results: Lobeline bound efficiently to the active site of DPP IV enzyme and consumed less binding energy than Sitagliptin. This finding was confirmed by the in vivo study. Administration of lobe line at a dose of 25 mg/kg in HFD/alloxan induced diabetic mice produced a significant reduction in blood glucose level and in DPP IV activity compared to the diabetic control group (P value> .01). Conclusion: Lobe line could be a good candidate to be developed as a natural compound for treating diabetes mellitus.

The hydro-distilled leaves of Pistacia lentiscus are considered as an agricultural residue and of no commercial value yet. In this study, chromatographic purification of a methanolic fraction of P. lentiscus L. (lentisk) distilled leaves yielded pure compounds, including Quercitrin (QUE) and Loliolid (LOL) which are characterized, for the first time, in the lentisk leaves’ residue. The inhibitory potential of QUE and LOL was investigated against tyrosinase and acetylcholinesterase activities using enzymatic assays and lysozyme fibrillation through Thioflavin-T fluorescence assay. Their binding mode to Bovine Serum Albumin (BSA) was also assessed by several spectroscopic analyses. Results show that QUE was more potent to inhibit enzyme activity than LOL. Besides, the Thioflavin-T assay confirmed that only QUE was able to block the fibril formation at a concentration of 25 μg/mL. Furthermore, the BSA quenching mechanism by QUE and LOL is a static process with conformational changes in BSA. Interestingly, our findings may provide novel insights into the potentiality of lentisk to be used as a bioresource for the generation of Quercitrin and Loliolid which can be commercially exploited in the field of cosmeceuticals and nutraceuticals.

Leishmaniasis still stands as one of the most prevalent neglected tropical diseases in the least developed and emerging countries. The recommended therapeutic arsenal to treat leishmaniasis is characterized by several shortcomings, and resistance has already been reported. Hence, this dramatic background highlights the pressing need to develop novel, affordable, and safe antileishmanial drugs. Multiple classes of natural compounds have been reported to possess antileishmanial activity. Among these classes, iridoids stand out as a special type of monoterpenoids with diverse biological properties—including their antileishmanial potential. This review aims to discuss the available literature between 1991 and 2020 related to the antileishmanial activity of the iridoid class. Throughout the past decades, various investigations attributed antileishmanial action to assorted iridoid types, including inhibitory potential towards validated drug targets and immunomodulatory activity. The latter deserves special attention due to the ability of some iridoids to improve the host’s immune response against parasites. It opens the possibility of iridoids become adjuncts in leishmaniasis treatments by improving the efficacy of currently employed drugs. Furthermore, the present study intends to provide a convenient visual representation of which iridoids and Leishmania spp. species have been most investigated as a guide for further researches.

Aim/Background: Dietary factors have shown important role in the rapid management of several human ailments including viral infections Since ancient times, constituents of Nigella sativa seeds have been utilized as food preservatives with significant medicinal benefits in Unani and Ayurveda practices Nigella sativa (Black seed) has presented significant therapeutic potential against several disorders and known to have numerous biological activities (such as antibacterial, antiviral and anti-inflammatory) Nigella plant has shown significant potential in the reduction of viral load as well as in enhancing immunity Materials and Methods: Our study enlightens the inhibitory role of phytocompounds of Nigella sativa against various key targets of coronavirus through in silico approaches including molecular docking using several software’s such as AUTO DOCK 4 2 and PATCH DOCK Results: Thus in this study, we have elucidated the potential of best reported phytocompounds of Nigella sativa as potent inhibitors of COVID-19 We have mainly focused our study towards inhibiting four different targets in CoVs Molecular docking was performed between 10 potent compounds to identify best potential inhibitor which could inhibit the viral attachment and replication Nigellone have shown the most significant inhibitory potential (with Binding energy of-5 48) against all the four crucial targets of coronavirus Conclusion: Further, in vitro experiments are needed to validate the efficacy of Nigellone as a potential lead compound for the management of COVID-19 disease © 2021, Association of Pharmaceutical Teachers of India All rights reserved

Ferula assafoetida is a part of many herbal formulations and hence it is pertinent to check the safety of its components specially to growing embryos. Zebrafish (Danio rerio) is considered to be one of the best models to study human embryonic development and metabolic pathways as its genome is fully sequenced and it possesses easily detectable developmental properties. In present study, the embryos of Danio rerio were treated with different concentrations of methanolic extract of Ferula assafoetida (MEFA) and its effects were checked at different post fertilization periods. Decreased heart beat rates, shrinkage of the chorion wall and other developmental abnormalities leading to the death of the embryos were observed. The methanolic extract of Ferula assafoetida was subjected to GC-MS to determine the different compounds present. Cardiotoxicity of these compounds were studied as it is one of the important factors for the retraction of a drug from the market. Molecular docking studies with L-type calcium channel (LTCC), a protein important for cardiac functioning, showed strong binding to the phytochemicals in the extract, with the maximum binding affinity observed with 26-hydroxycholesterol. The study proves that the methanolic extract of Ferula assafoetida contains phytochemicals which have the potential to cause cardiotoxicity in zebrafish embryos by interfering with the functions of LTCC possibly leading to arrhythmia. Altogether, our data suggest that the usage of these extracts in drug formulations should be done with caution. This is also indicative of the possible cytotoxic effect of the extract which could be tapped in the search for anticancer drugs.

Bacterial resistance to antibiotics and host defense systems is primarily due to bacterial biofilm formation in antibiotic therapy. In the present study, two complexes, bis (biphenyl acetate) bipyridine Cu (II) (1) and bis (biphenyl acetate) bipyridine Zn (II) (2), were tested for their ability to prevent biofilm formation. The minimum inhibitory concentration and minimum bactericidal concentration of complexes 1 and 2 were 46.87 ± 1.822 and 93.75 ± 1.345 and 47.87 ± 1.345 and 94.85 ± 1.466 μg/mL, respectively. The significant activity of both complexes was attributed to the damage caused at the membrane level and was confirmed using an imaging technique. The biofilm inhibitory potential levels of complexes 1 and 2 were 95% and 71%, respectively, while the biofilm eradication potential levels were 95% and 35%, respectively, for both complexes. Both the complexes showed good interactions with the E. coli DNA. Thus, complexes 1 and 2 are good antibiofilm agents that exert their bactericidal actions possibly by disrupting the bacterial membrane and interacting with the bacterial DNA, which can act as a powerful agent to restrain the development of bacterial biofilm on therapeutic implants.

The pandemic caused by the new coronavirus has resulted in a global health emergency and has prompted an urgent need for new treatment strategies. No target-specific drugs are currently available for SARS-CoV-2, but new drug candidates targeting the viral replication cycle are being explored. A prime target of drug-discovery efforts is the SARS-CoV-2 main protease (Mpro). In this work, we identified a potential inhibitor for SARS-CoV-2 main protease using in silico methodologies. Molecular docking and molecular dynamics studies were carried out to ascertain the inhibitory action of α and β anomers of Punicalagin from fruit peel of Punica granatum against the Mpro protease. The molecular dynamics results revealed that the β-anomeric configuration of punicalagin allowed access to more hydrogen bonds and hydrophobic interaction leading to higher selectivity and specificity of β-anomer than α-anomer. Therefore, the β-anomer of Punicalagin could act as potential inhibitor against the main protease of SARS-CoV-2 and may act as a potential drug candidate.

Medicinal plants are widely used in nonindustrialized societies and developing countries in Africa, Asia, and South America because they are cheaper and more accessible than modern drugs. Medicinal and food plants that are traditionally used as dietary adjuvants to improve health have been evaluated, interalia, for their blood glucose lowering potential, both in vitro and in vivo. The main aim was to preevaluate the extracts or the respective carbohydrate fractions for any potential α-amylase and α-glucosidase inhibitory activity in vitro. An additional aim was to confirm the inhibitory potential of the new raw materials in vivo. Furthermore, other crude extracts significantly inhibiting in vitro the possibility of lowering postprandial glucose were assessed. It is expected that further scientific research can confirm the rationality of selected species of food and medicinal plants as potential dietary additives.

Amyloidogenic protein assembly into insoluble fibrillar aggregates is linked with several neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease, affecting millions of people worldwide. The search for a potential anti-amyloid drug has led to the discovery of hundreds of compounds, none of which have passed all clinical trials. Gallic acid has been shown to both modulate factors leading to the onset of neurodegenerative disorders, as well as directly inhibit amyloid formation. However, the conditions under which this effect is seen could lead to oxidation of this polyphenol, likely changing its properties. Here we examine the effect of gallic acid and its oxidised form on the aggregation of a model amyloidogenic protein–insulin at low pH conditions. We show a vastly higher inhibitory potential of the oxidised form, as well as an alteration in the aggregation pathway, leading to the formation of a specific fibril conformation.

Integrase (IN) strand transfer inhibitors (INSTIs) are recent compounds in the antiretroviral arsenal used against HIV. INSTIs work by blocking retroviral integration; an essential step in the viral lifecycle that is catalyzed by the virally encoded IN protein within a nucleoprotein assembly called an intasome. Recent structures of lentiviral intasomes from simian immunodeficiency virus (SIV) and HIV have clarified the INSTI binding modes within the intasome active sites and helped elucidate an important mechanism of viral resistance. The structures provide an accurate depiction of interactions of intasomes and INSTIs to be leveraged for structure-based drug design. Here, we review these recent structural findings and contrast with earlier studies on prototype foamy virus intasomes. We also present and discuss examples of the latest chemical compounds that show promising inhibitory potential as INSTI candidates.

To date, no studies have investigated the phytochemical screening and biological activities of Cachrys libanotis L. traditionally used for the treatment of gout and rheumatism. Therefore, we aimed to investigate, for the first time, the phytochemical contents, the xanthine oxidoreductase inhibition, antibacterial, and antioxidant activities of extracts derived from the roots of C. libanotis L. Roots were submitted to extraction and fractionation using three different solvents sequentially, in the ascending order of polarity. Subsequently, XOR was purified from bovine milk and its inhibition was evaluated using xanthine/XOR system. The antioxidant activities were assessed employed superoxide scavenging, β- carotene bleaching, DPPH scavenging, ferrous iron chelation and FRAP assays). The antibacterial activity was tested by disc diffusion assay against 11 ATCC strains. Extraction and fractionation gave crude extract (CrE), hexane extract (HxE), chloroform extract (ChE), ethyle acetate extract (EAE) and aqueous extract (AqE). EAE exhibited the highest XOR inhibitory effect. CrE exhibited the highest effect as DPPH scavenger. All fractions exhibited a good activity against linoleate oxidation. Both CrE and AqE had an excellent chelating activity. Extracts showed a medium reducing power with greatest value exhibited by EAE. The plant extracts exhibited moderate to good antibacterial activity where the HxE extract had the strongest antimicrobial activity. From the obtained results, C. libanotis roots might be helpful in preventing or slowing the progress of gout, and it could be used as an additive in the food industry providing good protection against oxidative damage. Keywords: Cachrys libanotis, polyphenols, oxidative stress, xanthine-oxidoreductase (XOR), antimicrobial.

Eleutherococcus senticosus (Rupr. & Maxim.) Maxim., popularly known as ‘Siberian ginseng’, is an important medicinal plant. Pharmacologically active compounds of this plant are called eleutheroside...

The aim of this study was to evaluate the in-vitro inhibitory potential of various leaf extracts of Justicia carnea on alpha-amylase and alpha-glucosidase activities and the anti-diabetic activity of the ethanol leaf extract using albino wistar rats. The analyses were carried out using standard biochemical methods. The oral acute toxicity test (LD50) in rats of the ethanol leaf extract was determined using Lorke’s method. Diabetes was induced in the rats by a single intraperitoneal dose of 120 mg/kg. b.w of alloxan. Six (6) experimental groups of rats (n=6) were used for the study. Three groups of diabetic rats received oral daily doses of 200 mg/kg, 400 mg/kg and 600 mg/kg ethanol leaf extract of Justicia carnea respectively while gilbenclamide (5 mg/ml); a standard diabetic drug was administered to a specific group. Treatment lasted for 14 days. From the results of the in-vitro inhibitory activity, the different extracts of Justicia carnea demonstrated dose dependent strong inhibitory activity against α-amylase but moderate inhibitory activity against α-glucosidase. The ethanol leaf extract was the most potent inhibitor of both α-amylase and α-glucosidase in comparison with other extracts and acarbose; the standard. The ethanol leaf extract exhibited maximum of 82.18% inhibition with IC50 of 2.99 ± 1.14 mg/ml for α-amylase and 41.66% with IC50 of 9.66 mg/ml ± 0.32 mg/ml for α-glucosidase. From the analysis of the Lineweaver-Burk plot, the ethanol leaf extract exhibited mixed noncompetitive inhibition of α-amylase and competitive inhibition of α-glucosidase activities. The acute toxicity study showed that the extract had an LD50 > 5000 mg/kg. From the result of the anti-diabetic study, the fasting blood glucose levels significantly (p

Human Immunodeficiency Virus (HIV), the etiological agent for Acquired Immunodeficiency Syndrome (AIDS), continues to kill humans despite stupendous advances in antiviral research. With the presently available combination antiretroviral therapeutic arsenal, AIDS is now a manageable disease but with no cure available till date. The development of novel antivirals consumes an extensive amount of time and resources. Hence, repurposing of the established gold standard molecules for their anti-HIV application is enormously advantageous. In this study, we report that N-p-Tosyl-L-phenylalanine chloromethyl ketone (TPCK) inhibits HIV-1 replication in a highly-conserved manner. Further, TPCK inhibits HIV-1 replication at the late stages of its life cycle by impeding viral protease (PR) enzyme activity. Additionally, our results demonstrate that the combination of TPCK with established HIV-1 PR inhibitors shows significant synergistic inhibitory potential, suggesting the potential use of TPCK in cART regimen. Collectively, we report the anti-HIV activity of TPCK, which should be further characterized for its translational applications.

Two new haemanthamine-type alkaloids, crinasiaticine A (1) and crinasiaticine B (2), along with fifteen known alkaloids 3–17, were isolated from the bulbs of Crinum asiaticum L. var. asiaticum. The structures of the new compounds were established by spectroscopic analysis and the known compounds were identified by spectral comparison with those previously reported. All of the compounds were evaluated for their inhibitory potential against human carbonic anhydrase isozyme II (hCAII) in vivo activity using a novel yeast-based assay. Compounds 5 and 15 inhibited hCAII activity with minimal effective doses of 166 and 8.7 μM, respectively. These two compounds did not show cytotoxicity, even at the high concentration used.

Background: In the current study, we present an integrated in silico cheminformaticsmolecular docking approach to screen and test potential therapeutic compounds against viruses. Fluoroquinolones have been shown to inhibit HCV replication by targeting HCV NS3-helicase. Based on this observation, we hypothesized that natural analogs of fluoroquinolones will have similar or superior inhibitory potential while having potentially fewer adverse effects. Methods: To screen for natural analogs of fluoroquinolones, we devised an integrated in silico Cheminformatics-Molecular Docking approach. We used 17 fluoroquinolones as bait reference, to screen large databases of natural analogs. 10399 natural compounds and their derivatives were retrieved from the databases. From these compounds, molecules bearing physicochemical similarities with fluoroquinolones were analyzed using a cheminformatics-docking approach. Results: From the 10399 compounds screened using our cheminformatics approach, only 20 compounds were found to share physicochemical similarities with fluoroquinolones, while the remaining 10379 compounds were physiochemically different from fluoroquinolones. Molecular docking analysis showed 32 amino acids in the HCV NS3 active site that were most frequently targeted by fluoroquinolones and their natural analogues, indicating a functional similarity between the two groups of compounds. Conclusion: This study describes a speedy and inexpensive approach to complement drug discovery and design against viral agents. The in silico analyses we used here can be employed to shortlist promising compounds/putative drugs that can be further tested in wet-lab.

Facts over microorganisms to predominate periodontitis, shifting of human microbiota by Dimocarpus longan (D. longan) plant, and potentiation of antimicrobial activity by biosynthetic silver nanoparticles (SNPs) intended present study to biosynthesize, optimize, characterize and evaluate the antimicrobial potential of silver nanoparticles (SNPs) obtained using D. longan leaves aqueous extract (DLLAE). Study involved preparation of DLLAE using decoction method. The DLLAE was subjected to biosynthesis of SNPs followed by optimization (using UV-Visible spectrometry), characterization (by FTIR, FESEM, XRD, and EDX), stability, and antimicrobial activity of SNPs against periodontitis triggering human microflora. Biosynthesized SNPs exhibited signal between 416-453 nm. Optimization study established AgNO3 concentration (5 mM), pH 4, DLLAE and AgNO3 ratio (1:9) and temperature (60°C) as parametric requirement for SNPs biosynthesis using DLLAE. Stability study exhibited signal between 489-553 nm supporting SNPs stability. Characterization data of FESEM showed that SNPs were poly dispersed, and spherical shaped. Biosynthesized SNPs size ranged from 74.82 nm to 131.5 nm. The XRD data revealed presence of signals at 38.08°, 44.33°, 64.47°, and 78.83° 2θ values indexed to silver cubic structure planes. In EDX study, silver exhibited strong signal (55.54%). Antimicrobial investigation explored the high inhibitory potential of SNPs against B. subtilis and P. aeruginosa; and low inhibitory potential against S. aureus and E. coli. Present study conclude that biosynthesis of SNPs using DLLAE is an efficient method and biosynthetic SNPs possess high antimicrobial potential against P. aeruginosa and B. subtilis the periodontitis triggering pathogens.

Alzheimer's disease is a neurodegenerative disorder characterized by memory loss and impairment of language. Alzheimer's disease is strongly associated with oxidative stress and impairment in the cholinergic pathway, which results in decreased levels of acetylcholine in certain areas of the brain. Hence, inhibition of acetylcholinesterase activity has been recognized as an acceptable treatment against Alzheimer's disease. Nature provides an array of bioactive compounds, which may protect against free radical damage and inhibit acetylcholinesterase activity. This study compares the in vitro antioxidant and anticholinesterase activities of hydroalcoholic extracts of five cultivars of Rosa Damascena Mill. petals (R. damascena 'Bulgarica', R. damascena 'Faik', R. damascena 'Iranica', R. damascena 'Complex-635' and R. damascena 'Complex-637') from Isparta, Turkey. The antioxidant activities of the hydroalcoholic extracts were tested for ferric ion reduction and DPPH radical scavenging activities. The anti-acetylcholinesterase activity was also evaluated. All rose cultivars showed a high potency for scavenging free radical and inhibiting acetylcholinesterase activity. There was a significant correlation between antioxidant and acetylcholinesterase inhibitory activity. Among cultivars, Complex-635 showed the highest inhibitory effect with an IC50 value of 3.92 µg/mL. Our results suggest that all these extracts may have the potential to treat Alzheimer's disease with Complex-635 showing more promise.

As a way to investigate new antiviral leads against Zika virus (ZIKV), we have targeted the NS3 helicase (NS3H) protein with biscoumarin derivatives. The NS3H protein from ZIKV is important, as it plays a significant role in the viral genome replication process. We have assessed the NTPase modulatory effects of biscoumarin derivatives against the NTPase activity of NS3H through in vitro enzymatic studies. Subsequently, to explore the mechanism, detailed computational studies were conducted. The NS3H protein has two binding cavities: one is the NTPase binding cavity where ATP binds, and the other is an RNA binding cavity for the binding of RNA molecules. Biscoumarin derivatives were found to be efficient in binding to both cavities, i.e., the NTPase and RNA binding cavities of the NS3H protein. A biscoumarin derivative with the best binding affinity for the NTPase binding cavity and the lowest binding affinity for the RNA binding groove revealed the best in vitro NTPase inhibitory activity. Also, the biscoumarin derivative with the lowest binding affinity for the NTPase binding cavity and higher binding affinity for the RNA binding cavity revealed the worst NTPase inhibitory activity under the same in vitro assay conditions. Here, we concluded that biscoumarin derivatives are modulators of the NS3H protein and they can be considered as promising anti-viral lead molecules. The structural activity relationships (SARs) of the biscoumarin derivatives in relation to their NTPase inhibitory activities were established, and we reported two derivatives, namely MN-9 and MN-10, as potential NS3H–NTPase inhibitor molecules.

Starch-iodine assay method for the determination of α-amylase activity is also used in screening extracts for α-amylase inhibitors. However, there are indications that this method may not be appropriate for screening some classes of compounds or plant extracts. The present study investigated the limitation(s) of this method in screening plant extracts/compounds for α-amylase inhibition. A crude methanol extract (CR) of Dacryodes edulis, its solvent fractions (ethyl acetate (EA), aqueous methanol (AM), and hexane (HX)), quercetin (QC), and benzoic acid (BA) were used for this study. The phytochemical content and antioxidant activity were screened spectrophotometrically. α-Amylase inhibition (expressed in percentage and as IC50) was determined by starch-iodine method approach I and II (ST-ID I and ST-ID II, respectively) and dinitrosalicylic acid (DNSA) as the control method. The results showed that the extracts/compounds (AM, EA, and QC) with significantly high polyphenolic content, antioxidant activity, and starch-iodine complex decolorization effect yielded contrary results of α-amylase inhibition when the results of ST-ID I and II methods were compared to that of the DNSA method. The other test samples (CR, HX, and BA) yielded similar results for all the three methods. The result also showed the decolorization (%) of starch-iodine complex by the test samples correlated significantly (r = 0.877, P < 0.05) with DPPH reduction (%). In conclusion, the present study showed that the starch-iodine method is not appropriate for screening antioxidative extracts/compounds for α-amylase inhibitors – they decolorize the assay reagent in a manner similar to DPPH reduction and hence confound the result.

Fermentation liquid from mangrove leaves Avicennia marina contains microorganisms, nutrients, and secondary metabolites. This study aimed to identify bacteria and the compounds in fermentation liquid of mangrove leaves A. marina and measured their inhibitory capacity against pathogenic bacteria Stenotrophomonas maltophilia which causes ice-ice disease in seaweed. Molecular analysis which aimed the 16S rRNA gene showed that the bacteria in fermentation liquid consisted of eight types of Bacillus, Bacillus subtilis MSAR-01, Bacillus megaterium MSAR-02, Bacillus firmus MSAR-03, Bacillus thuringiensis MSAR-04, Bacillus subterranerus MSAR-05, Bacillus vietnamensis MSAR-06, Bacillus sp. MSAR-07, Bacillus circulans MSAR-08, with the best inhibitory power indicated by B. subtilis MSAR-01, B. vietnamensis MSAR-06, and Bacillus sp. MSAR-07. The administration of lactic acid, bacteriocin, total fermentation liquid, and supernatant as much as 15 mL produce inhibition to S. maltophilia indicated better result than using one or a combination of several types of bacterial isolates. The inhibition of single bacterial enriched fermentation and supernatant liquids was better than bacterial combination enrichment. Keywords: Avicennia marina, fermentation, ice-ice, mangrove

Chickpea wilt is one of the major limiting factors, for low yield of chickpea. In Pakistan chickpea wilt causes 10-50% losses every year. At all concentrations, Carbendazim and Benomyl proved most effective while Acrobat was least effective in suppressing the mycilial growth of the Fusarium oxysporum f. sp. ciceri. However, higher concentration of Acrobat was also slightly effective. Among the plant extracts, higher concentrations of Sufaida and Neem proved to be effective while onion failed to control the colony growth of Fusarium oxysporum f.sp. ciceri at all concentrations.

The HIV-1 protease plays an essential role in the replication cycle of HIV-1; therefore there is a direct need to develop novel inhibitors of the HIV-1 protease, which can cease the viral replication. The present study targets the discovery of potential inhibitors of HIV-1 protease from a set of phytochemicals. From 2505 phytochemicals, 108 compounds were docked, after screening, with the HIV-1 protease to analyze their inhibitory potential against the protease. DFT analysis was also conducted to study the reactivity of strongly docked compounds. Out of 108 phytochemicals, 38 compounds showed binding affinity greater than the desired threshold. Reactivity of these 38 inhibitors was also high as compared to other compounds, based on the DFT results. These results suggest that the selected 38 phytochemicals are drug candidates and they have the potential to be effectively used against HIV in the future.

Anthocyanins and other polyphenols are responsible for the positive effects that consumption of tart cherries and their products has on human health. However, instability of these compounds under processing conditions is a significant problem for fruit processing industry. The aim of this study was to investigate the possibility of using carboxymethylcellulose (CMC) hydrogels for the delivery of the tart cherry polyphenols. For this purpose hydrogels with tart cherry juice (TJ) and 2%, 3%, 4% and 5% (w/w) of CMC were prepared. Total phenolics, proanthocyanidins and monomeric anthocyanins as well as individual phenolics were determined. Antioxidant capacity (CUPRAC, DPPH and ABTS assays) and inhibitory potential against two enzymes, α-amylase and α-glucosidase were evaluated, as well. It was observed that hydrogel with 4% CMC (w/w) had the highest retention ability of phenolics (63%) and anthocyanins (80%) throughout preparation of hydrogels. That hydrogel also had the highest antioxidant potential. Results of this study showed that proper formulation of food systems is important in order to maximize retention of anthocyanins and other valuable polyphenols.

Essential oils and aromatic extracts (oleoresins, absolutes, concretes, resinoids) are often used as food flavorings and constituents of fragrance compositions. The flavor and fragrance industry observes significant growth in sales of some natural materials during the COVID-19 outbreak. Some companies worldwide are making false claims regarding their essential oils or blends to be effective (or indirectly points towards this conclusion) against coronaviruses even though the available data on the activity of plant materials against highly pathogenic human coronaviruses is very scarce. Our exploratory study aimed to develop pioneering knowledge, and provide the first experimental results on the inhibitory properties of hundreds of flavor & fragrance materials against SARS-CoV-2 main- and papain-like proteases. As essential oils are volatile products, they could provide an interesting subsidiary inhalation therapeutic strategy in the long term.

Ispitan je inhibitorni potencijal odabranih probiotičkih proizvoda na određene bakterije: Escherichia coli, Salmonella typhimurium, Enterococcus faecalis i Staphylococcus aureus. Probiotici su kulture živih stanica mikroorganizama koje djeluju korisno na domaćina poboljšavajući svojstva autohtone mikroflore probavnog sustava domaćina. E. coli i S. typhimurium pripadaju razredu Gammaproteobacteria (porodica Enterobacteriaecae), dok se E. faecalis i S. aureus nalaze u razredu Bacilli (porodice Enterococcaceae te Staphylococcaceae). Od odabranih probiotičkih proizvoda, jedino je fermentirano mlijeko Tibetanskom gljivom uzrokovalo potpunu zonu inhibicije i to kod gram negativnih bakterija: E. coli i S. typhimurium. Fortia (Vindija) je jedini fermentirani probiotički napitak koji je uzrokovao djelomičnu inhibiciju rasta S. aureus. Niti jedan probiotički proizvod nije uzrokovao inhibiciju E. faecalis. Inhibitory potential of selected fermented probiotic product was analyzed on test bacteria: Escherichia coli, Salmonella typhimurium, Enterococcus faecalis and Staphylococcus aureus. Probiotics are live microbial cultures having beneficiary effect on host improving host`s digestive tract microflora. E. coli and S. typhimurium are systemized in class Gammaproteobacteria (family Enterobacteriacease) while E. faecalis and S. aureus are in class Bacilli (family Enterococcaceae and Staphylococcaceae, respectively). Of selected probiotics, only Tibetan mushroom fermented milk exhibited full inhibition zone on Gram negative E. coli and S. typhimurium. On S. aureus only Fortia (Vindija) displayed partial inhibition of inoculated cells. None of the tested probiotics was inhibitory on E. faecalis.

Herein, we report the synthesis and inhibitory potential of indazole (Methyl 1H-indazole-4-carboxylate) derivatives (1–13) against α-amylase and α-glucosidase enzymes. The described derivatives demonstrated good inhibitory potential with IC50 values, ranging between 15.04 ± 0.05 to 76.70 ± 0.06 µM ± SEM for α-amylase and 16.99 ± 0.19 to 77.97 ± 0.19 µM ± SEM for α-glucosidase, respectively. In particular, compounds (8–10 and 12) displayed significant inhibitory activities against both the screened enzymes, with their inhibitory potential comparable to the standard acarbose (12.98 ± 0.03 and 12.79 ± 0.17 µM ± SEM, respectively). Additionally, the influence of different substituents on enzyme inhibition activities was assessed to study the structure activity relationships. Molecular docking simulations were performed to rationalize the binding of derivatives/compounds with enzymes. All the synthesized derivatives (1–13) were characterized with the aid of spectroscopic instruments such as 1H-NMR, 13C-NMR, HR-MS, elemental analysis and FTIR. Communicated by Ramaswamy H. Sarma

The green synthesis of gold nanoparticles (Au NPs) from their precursor was carried out using Delphinium uncinatum and Erythrophyleum guineense plants extracts. The Au NPs obtained were characterized by various instrumental techniques such as scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction (XRD) and UV/Visible (UV/VIS) spectrophotometer. The SEM study presented that E. guineense (GE) and D. uncinatum (GN) synthesized gold nanoparticles was below 100 and 300 nm, respectively. The micrographs also presented that E. guineense (GE) synthesized gold particles had irregular round shaped while the D. uncinatum (GN) synthesized nanoparticles had cylindrical shaped. The XRD spectra presented peaks at about 38.1°, 44.43°, 64.6° and 77.64° can be indexed to (111), (200), (220) and (311) orientation, respectively, which confirmed the presence of gold nanoparticles. It means that both E. guineense (GE) and D. uncinatum (GN) synthesized gold nanoparticles are highly crystalline. The UV/VIS analysis presented that both plant extracts significantly reduced the gold slat and as a result high quantity of gold nanoparticles were formed. The E. guanense gold NP and D. uncinatum gold NPs were investigated for their in-vitro cholinesterases inhibitory potentials in 62.5-1000 µg/mL concentrations range. The bioactivity results presented that the loading of the test samples in gold NPs enhanced their AChE and BChE inhibitory potentials. Resumen. La síntesis verde de nanopartículas de oro (NP de Au) se llevó a cabo mediante extractos de plantas de Delphinium uncinatum y Erythrophyleum guineense. Las NP de Au obtenidas se caracterizaron mediante diversas técnicas instrumentales como microscopía electrónica de barrido (SEM), dispersión de energía de rayos X (EDX), difracción de rayos X (XRD) y espectrofotómetro UV / Visible (UV / Vis). El estudio SEM reveló tamaños de las nanopartículas de oro sintetizadas por E. guineense (GE) y D. uncinatum (GN) por debajo de 100 y 300 nm, respectivamente. Las micrografías también mostraron que las partículas de oro sintetizadas por E. guineense (GE) tenían una forma redonda irregular, mientras que las nanopartículas sintetizadas por D. uncinatum (GN) tenían una forma cilíndrica. Los patrones XRD presentaron picos a aproximadamente 38.1 °, 44.43 °, 64.6 ° y 77.64 ° pueden indexarse ​​a la orientación (111), (200), (220) y (311), respectivamente, lo que confirmó la presencia de nanopartículas de oro cristalinas. El análisis UV / Vis mostró que ambos extractos de plantas formaron nanopartículas de oro. Se investigaron las NP de oro como inhibidores de colinesterasas in vitro en un intervalo de concentraciones de 62.5 a 1000 µg / ml. Los resultados de la bioactividad mostraron que la carga de las muestras de prueba en NP de oro mejoró sus potenciales inhibidores de AChE y BChE.