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There has been a lot of interest in using naturally occurring substances to treat a wide variety of chronic disorders in recent years. From the gum resin of Boswellia serrata and Boswellia carteri, the pentacyclic triterpene molecules known as boswellic acid (BA) are extracted. We aimed to provide a detailed overview of the origins, chemistry, synthetic derivatives, pharmacokinetic, and biological activity of numerous Boswellia species and their derivatives. The literature searched for reports of B. serrata and isolated BAs having anti-cancer, anti-microbial, anti-inflammatory, anti-arthritic, hypolipidemic, immunomodulatory, anti-diabetic, hepatoprotective, anti-asthmatic, and clastogenic activities. Our results revealed that the cytotoxic and anticancer effects of B. serrata refer to its triterpenoid component, including BAs. Three-O-acetyl-11-keto-BA was the most promising cytotoxic molecule among tested substances. Activation of caspases, upregulation of Bax expression, downregulation of nuclear factor-kappa B (NF-kB), and stimulation of poly (ADP)-ribose polymerase (PARP) cleavage are the primary mechanisms responsible for cytotoxic and antitumor effects. Evidence suggests that BAs have shown promise in combating a wide range of debilitating disease conditions, including cancer, hepatic, inflammatory, and neurological disorders., (© 2023. The Author(s).)

Antidiabetic activity of methanolic extract, petroleum ether, ethyl acetate and n -butanol fractions of Ipomoea cairica (L.) Sweet leaves was performed in-vitro using α -glucosidase and α -amylase inhibition methods. Phytochemical study of the ethyl acetate fraction which possessed the highest antidiabetic activity led to isolation of five flavonoids for the first time from this plant, including two rare flavonoid sulphates, ombuin-3-sulphate [ 1 ] and rhamnetin-3-sulphate [ 2 ] and three flavonoid glycosides, kaempferol 7- O - α -L-rhamnopyranoside [ 3 ], kaempferol 3,7-di- O - α -L-rhamnopyranoside [ 4 ] and quercetin 3- O - α -L-arabinopyranoside [ 5 ]. The 1 H and 13 C NMR of 1 and 13 C NMR of 2 , were reported here for the first time. Compounds [ 1 - 4 ] showed a concentration-dependent in-vitro inhibitory activity against α- glucosidase and α- amylase. Furthermore, in-silico study predicted that compounds ( 1 - 5 ) showed good interactions with α- glucosidase, α- amylase, and protein tyrosine phosphatase 1b.

Methanolic extracts of Gleditsia triacanthos L. fruits and Gleditsia caspica Desf. leaves yielded two mono-carbonyl curcumin analogues; (1 E ,4 E )-1,5- bis (4-hydroxy-3-methoxyphenyl)penta-1,4-dien-3-one [ 1 ], (1 E ,4 E )-1,5- bis (4-hydroxyphenyl)penta-1,4-dien-3-one [ 2 ], in addition to β -sitosterol [ 3 ], apigenin [ 4 ], quercetin-3`- O -methyl ether [ 5 ], rutin [ 6 ], quercetin [ 7 ], naringenin [ 8 ], eriodictyol [ 9 ], vitexin [ 10 ], isovitexin [ 11 ], gleditsin A [ 12 ]. The isolation of these compounds was reported here for the first time from the named plants. The separation and identification of curcumin analogues from genus Gleditsia in addition to 13 C NMR data of compound 2 were reported here for the first time. Compounds 1 and 2 were assayed in two hepatic cancer cells; HepG-2 and Huh-7. Compound 1 showed high cytotoxic activity against HepG-2 with an IC 50 value of 14.39 µM, compared with the standard, IC 50 = 12.44 μM.

The target mono- and bis-(6-pyrazolyltriazolo-thiadiazine) derivatives 4a-c and 6a-d were synthesized using a straightforward protocol via reaction of 3-bromoacetylpyrazole 2 with 4-amino- s -triazole-3-thiols 3a-c and bis(4-amino-5-mercapto- s -triazol-3-yl)alkanes 5a-d , respectively. The bis(6-pyrazolyl- s -triazolo[3,4- b ][1,3,4]thiadiazine) derivatives 8a , b and 10 were also constructed by reaction of the triazolo[3,4- b ][1,3,4]thiadiazine-3-thiol 4c with the proper dibromo compounds 7a , b and 9 , respectively. Structures of the new substances were determined by spectroscopic and analytical data. Compounds 4b , 4c , and 6a showed potent cytotoxicity against MCF-7 (IC 50 = 3.16, 2.74, and 0.39 μM, respectively) and were safe against the MCF-10A cells. Compounds 4b , 4c , and 6a also showed promising dual EGFR and CDK-2 inhibition activities, particularly 6a was the most effective (IC 50 = 19.6 and 87.9 nM, respectively), better than Erlotinib and Roscovitine. Compound 6a treatment induced EGFR and CDK-2 enzyme inhibition by 97.18% and 94.11%, respectively, at 10 μM (the highest concentration). Compound 6a notably induced cell apoptosis in MCF-7 cells, increasing the cell population by total apoptosis 43.3% compared to 1.29% for the untreated control group, increasing the cell population at the S-phase by 39.2% compared to 18.6% (control)., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: 1,3-Diphenylpropane-1,3-dione (1) is an acetylacetone β-diketone in which both of the methyl groups have been replaced with phenyl groups. It is a component of licorice root extract (Glycyrrhiza glabra) and has anti-mutagenic and anti-cancer properties. It functions as a metabolite, an anti-mutagen, and an anti-neoplastic agent. It is an aromatic ketone and a β-diketone. 1,3-Diphenylpropane-1,3-dione (1) is primarily used in PVC hard and soft materials, including plates, films, profiles, pipes, and fittings., Objectives: This research aims to examine the utility of 1,3-diphenylpropane-1,3-dione (1) for the synthesis of a variety of new heterocyclic compounds, such as thioamide, thiazolidine, thiophene-2-carbonitrile, phenylthiazole, thiadiazole-2-carboxylate, 1,3,4-thiadiazole derivatives, 2-bromo-1,3-diphenylpropane-1,3-dione, new substituted benzo[1,4]thiazines, phenylquinoxalines, and imidazo[1,2-b][1,2,4]triazole derivatives of potential biological activity Methods: 1,3-Diphenylpropane-1,3-dione (1) was used as a starting compound for the synthesis of 3-oxo-N,3-diphenyl-2-(phenylcarbonyl)propanethioamide (3) and 2-bromo-1,3-diphenylpropane-1,3-dione (25), which can be used for further preparations. The 5α-reductase inhibitor activity of some of the synthesized compounds was also tested in vivo; the ED50 and LD50 data were established, Results: Using IR, 1H-NMR, mass spectroscopy, and elemental analysis, the structures of all produced compounds were elucidated. Some of these prepared compounds were reported as 5α-reductase inhibitors., Conclusion: New heterocyclic compounds can be formed via 1,3-diphenylpropane-1,3-dione (1), and some of these compounds can act as 5α-reductase inhibitors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

3-Bromoacetyl-4-(2-naphthoyl)-1-phenyl-1H-pyrazole (6) was synthesized from 2-acetylnaphthalene and was used as a new key building block for constructing the title targets. Thus, the reaction of 6 with the thiosemicarbazones 7a-d and 9-11 afforded the corresponding simple naphthoyl-(3-pyrazolyl)thiazole hybrids 8a-d and 12 ~ 14. The symmetric bis-(2-naphthoyl-pyrazol-3-yl)thiazol-2-yl)hydrazono)methyl)phenoxy)alkanes 18a-c and 21a-c were similarly synthesized from reaction of 6 with the appropriate bis-thiosemicarbazones 17a-c and 19a-c, respectively. The synthesized two series of simple and symmetrical bis-molecular hybrid merging naphthalene, thiazole, and pyrazole were evaluated for their cytotoxicity. Compounds 18b,c and 21a showed the most potent cytotoxicity (IC 50  = 0.97-3.57 µM) compared to Lapatinib (IC 50  = 7.45 µM). Additionally, they were safe (non-cytotoxic) against the THLE2 cells with higher IC 50 values. Compounds 18c exhibited promising EGFR and HER-2 inhibitory activities with IC 50  = 4.98 and 9.85 nM, respectively, compared to Lapatinib (IC 50  = 6.1 and 17.2 nM). Apoptosis investigation revealed that 18c significantly activated apoptotic cell death in HepG2 cells, increasing the death rate by 63.6-fold and arresting cell proliferation at the S-phase. Compound 18c upregulated P53 by 8.6-fold, Bax by 8.9-fold, caspase-3,8,9 by 9, 2.3, and 7.6-fold, while it inhibited the Bcl-2 expression by 0.34-fold. Thereby, compound 18c exhibited promising cytotoxicity against EGFR/HER2 inhibition against liver cancer., (© 2023. The Author(s).)

Soft corals distributed across the Red Sea coasts are a rich source of diverse and bioactive natural products. Chemical probing of the Red Sea soft coral Litophyton arboreum led to isolation and structural characterization of an undescribed sesquiterpenoid, litoarbolide A ( 1 ), along with 14 previously reported metabolites ( 2-15 ). The chemical structures of the isolates were assigned based on NMR as well as high resolution electrospray ionization mass spectrometry (HR-ESI-MS) data. Litoarbolide A is supposed to be the biosynthetic precursor to other sesquiterpenoids, which formed via further post-translational modifications. Furthermore, these metabolites were evaluated for anti-malarial activity, where only the acyclic sesquiterpenoid of a sec -germacrane nucleus ( 7 ) showed an activity against chloroquine-sensitive (D6) and chloroquine-resistant (W2) strains of Plasmodium falciparum with IC 50 at 3.7 and 2.2 mg/mL, respectively. Moreover, the isolated metabolites were all non-toxic to the Vero cell line. These findings support the consideration of L. arboreum in further natural anti-malarial studies.

Six flavonoids present in Pulicaria jaubertii , i.e., 7,3'-di- O -methyltaxifolin ( 1 ), 3'- O -methyltaxifolin ( 2 ), 7- O -methyltaxifolin ( 3 ), taxifolin ( 4 ), 3- O -methylquercetin ( 5 ), and quercetin ( 6 ), were tested for their anticancer activities. The methylated flavonoids, compounds 1 - 3 and 5 , were evaluated for their anticancer activities in comparison to the non-methylated parent flavonoids taxifolin ( 4 ) and quercetin ( 6 ). The structures of the known compounds were reconfirmed by spectral analyses using 1 H and 13 C NMR data comparisons and HRMS spectrometry. The anticancer activity of these compounds was evaluated in colon cancer, HCT-116, and noncancerous, HEK-293, cell lines using the MTT antiproliferative assays. The caspase-3 and caspase-9 expressions and DAPI (4', 6-diamidino-2-phenylindole) staining assays were used to evaluate the apoptotic activity. All the compounds exhibited antiproliferative activity against the HCT-116 cell line with IC 50 values at 33 ± 1.25, 36 ± 2.25, 34 ± 2.15, 32 ± 2.35, 34 ± 2.65, and 36 ± 1.95 μg/mL for compounds 1 to 6 , respectively. All the compounds produced a significant reduction in HCT-116 cell line proliferation, except compounds 2 and 6 . The viability of the HEK-293 normal cells was found to be significantly higher than the viability of the cancerous cells at all of the tested concentrations, thus suggesting that all the compounds have better inhibitory activity on the cancer cell line. Apoptotic features such as chromatin condensation and nuclear shrinkage were also induced by the compounds. The expression of caspase-3 and caspase-9 genes increased in HCT-116 cell lines after 48 h of treatment, suggesting cell death by the apoptotic pathways. The molecular docking studies showed favorable binding affinity against different pro- and antiapoptotic proteins by these compounds. The docking scores were minimum as compared to the caspase-9, caspase-3, Bcl-xl, and JAK2., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

In the search for a new anti-MRSA lead compound, emodin was identified as a good lead against methicillin-resistant Staphylococcus aureus (MRSA). Emodin serves as a new scaffold to design novel and effective anti-MRSA agents. Because rational drug discovery is limited by the knowledge of the drug target, α-hemolysin of Staphylococcus aureus was used in this study because it has an essential role in Staphylococcus infections and because emodin shares structural features with compounds that target this enzyme. In order to explore emodin's interactions with α-hemolysin, all possible ligand binding pockets were identified and investigated. Two ligand pockets were detected based on bound ligands and other reports. The third pocket was identified as a cryptic site after molecular dynamics (MD) simulations. MD simulations were conducted for emodin in each pocket to identify the most plausible ligand site and to aid in the design of potent anti-MRSA agents. Binding of emodin to site 1 was most stable (RMSD changes within 1 Å), while in site 2, the binding pose of emodin fluctuated, and it left after 20 ns. In site 3, it was stable during the first 50 ns, and then it started to move out of the binding site. Site 1 is a possible ligand binding pocket, and this study sheds more light on interaction types, binding mode, and key amino acids involved in ligand binding essential for better lead design. Emodin showed an IC 50 value of 6.3 μg/mL, while 1, 6, and 8 triacetyl emodin showed no activity against MRSA. A molecular modeling study was pursued to better understand effective binding requirements for a lead.

A number of new 1,ω-bis((acetylphenoxy)acetamide)alkanes 5a-f were prepared then their bromination using NBS furnished the novel bis(2-bromoacetyl)phenoxy)acetamides 6a-f. Reaction of 6a-f with 4-amino-5-substituted-4 H -1,2,4-triazole-3-thiol 7a-d and with o -phenylenediamine derivatives 9a and b afforded the corresponding bis(1,2,4-triazolo[3,4- b ][1,3,4]thiadiazine) derivatives 8a-l and bis(quinoxaline) derivatives 10a-e in good yields. The cytotoxicity of the synthesized compounds as well as apoptosis induction through PARP-1 and EGFR as molecular targets was evaluated. Three compounds, 8d, 8i and 8l, exhibited much better cytotoxic activities against MDA-MB-231 than the drug Erlotinib. Interestingly, compound 8i induced apoptosis in MDA-MB-231 cells by 38-fold compared to the control arresting the cell cycle at the G2/M phase, and its treatment upregulated P53, Bax, caspase-3, caspase-8, and caspase-9 gene levels, while it downregulated the Bcl2 level. Compound 8i exhibited promising dual enzyme inhibition of PARP-1 (IC 50 = 1.37 nM) compared to Olaparib (IC 50 = 1.49 nM), and EGFR (IC 50 = 64.65 nM) compared to Erlotinib (IC 50 = 80 nM). These results agreed with the molecular docking studies that highlighted the binding disposition of compound 8i inside the PARP-1 and EGFR protein active sites. Hence, compound 8i may serve as a potential anti-breast cancer agent., Competing Interests: The authors declare that there is no conflict-of-interest text., (This journal is © The Royal Society of Chemistry.)

To develop a specific treatment against COVID-19, we investigated silymarin-chitosan nanoparticles (Sil-CNPs) as an antiviral agent against SARS-CoV-2 using in silico and in vitro approaches. Docking of Sil and CNPs was carried out against SARS-CoV-2 spike protein using AutoDock Vina. CNPs and Sil-CNPs were prepared by the ionic gelation method and characterized by TEM, FT-IR, zeta analysis, and the membrane diffusion method to determine the drug release profile. Cytotoxicity was tested on both Vero and Vero E6 cell lines using the MTT assay. Minimum binding energies with spike protein and ACE2 were -6.6, and -8.0 kcal mol -1 for CNPs, and -8.9, and -9.7 kcal mol -1 for Sil, respectively, compared to -6.6 and -8.4 kcal mol -1 respectively for remdesivir (RMV). CNPs and Sil-CNPs were prepared at sizes of 29 nm and 82 nm. The CC50 was 135, 35, and 110 μg mL -1 for CNPs, Sil, and Sil-CNPs, respectively, on Vero E6. The IC50 was determined at concentrations of 0.9, 12 and 0.8 μg mL -1 in virucidal/replication assays for CNPs, Sil, and Sil-CNPs respectively using crystal violet. These results indicate antiviral activity of Sil-CNPs against SARS-CoV-2., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Zinc coumarate and zinc caffeinate nanoparticles (ZnCoNPs, ZnCaNPs) affect different biological processes. This study aimed to evaluate the mitigating action of ZnCoNPs in combination with ZnCaNPs against liver damage induced by gamma rays (γ-rays). Rats were exposed to 7 Gy of γ-rays and then injected intraperitoneally (i.p) with ZnCoNPs [2U/rat/day (5 mg/kg)] and ZnCaNPs [2U/rat/day (15 mg/kg)] for 7 consecutive days. The results showed that irradiated rats treated with ZnCoNPs (5 mg/kg/body weight) in combination with ZnCaNPs (15 mg/kg/body weight) for 7 days had a significant increases in body weight, antioxidant levels, T helper cell 4 (cluster of differentiation 4 (CD4)), and T cytotoxic cell 8 (cluster of differentiation 8 (CD8)), associated with a marked decrease in lipid peroxidation (LP), nitric oxide(NOx), total free radicals concentrate (TFRC), and DNA fragmentation. There were positive alterations in the morphological state, hematological parameters and the cell cycle phases. Additionally, the histopathological study demonstrated an improvement in the liver tissue of irradiated rats after treatment. Thus, ZnCoNPs and ZnCaNPs could be used as natural mitigating agents to reduce the hazards of ionizing radiation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Four undescribed cembranoids, sarcoroseolides A-D ( 1-4 ) along with nine reported related cembranoids ( 5-13 ) were isolated from the soft coral Sarcophyton roseum . The chemical structures of sarcoroseolides A - D were elucidated by extensive 1 D and 2 D NMR as well as HR-ESIMS spectroscopic data. Moreover, the geometric and absolute configurations were assigned by the modified Mosher's method and/or NOESY experiments. The extract and the isolated metabolites were evaluated for their potential anti-inflammatory and cytotoxic activities.

Introduction: Tetanus is still a major health issue, especially in rural areas, and is associated with high morbidity and mortality rate. This study was conducted to describe the pattern of presentation and treatment outcome among adult patients infected with tetanus in our environment., Materials and Methods: This is a descriptive retrospective hospital-based study conducted in Wad Medani teaching hospital, central Sudan. A total of thirty-one patients were enrolled in this study in the period between January 2018 and December 2020., Results: Thirty-one patients were infected with tetanus during the study period. They were 23 (74.2%) males and 8 (25.8%) females with a male-to-female ratio of 2.875 : 1. Their ages ranged from 20 to 70 years, and most of them (48.4%) were free workers. Acute injuries were the most common portal of entry (64.51%), and commonly involved the lower limbs (48.38%). Lock jaw (54.8%), muscle spasm (51.6%), and neck pain and stiffness (45.2%) were the most common presentation. Supportive measures along with surgical toilet and debridement, human tetanus immunoglobulin, antibiotics, and muscle relaxants were initiated in all patients. The most common antibiotics used were Penicillin V and Ceftriaxone. A muscle relaxant was administered to aid in relieving the spasms. Complication rate was 61.29% and included pulmonary and cardiovascular complications. Fifteen patients died accounting for an overall mortality rate of 48.4%., Conclusions: Tetanus remains a disease with high morbidity and mortality. The unknown/incomplete vaccination status among study participants, inadequate management, and lack of equipped resources lead to a devastating outcome as in Sudan., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Mumen Abdalazim Dafallah et al.)

Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O -methylated flavonoids; 5,4'-dihydroxy-3,6,7-tri- O -methyl flavone (penduletin) ( 1 ), 5,3'-dihydroxy-3,6,7,4',5'-penta- O -methyl flavone ( 2 ), and 5-hydroxy-3,6,7,3',4',5'-hexa- O -methyl flavone ( 3 ) from Rhamnus disperma roots. Additionlly, four flavonoid glycosides; kampferol 7- O - α -L-rhamnopyranoside ( 4 ), isorhamnetin-3- O - β -D-glucopyranoside ( 5 ), quercetin 7- O - α -L-rhamnopyranoside ( 6 ), and kampferol 3, 7-di- O - α -L-rhamnopyranoside ( 7 ) along with benzyl- O - β -D-glucopyranoside ( 8 ) were successfully isolated. Complete structure characterization of these compounds was assigned based on NMR spectroscopic data, MS analyses, and comparison with the literature. The O -methyl protons and carbons of the three O -methylated flavonoids ( 1 - 3 ) were unambiguously assigned based on 2D NMR data. The occurrence of compounds 1 , 4 , 5 , and 8 in Rhamnus disperma is was reported here for the first time. Compound 3 was acetylated at 5-OH position to give 5- O -acetyl-3,6,7,3',4',5'-hexa- O -methyl flavone ( 9 ). Compound 1 exhibited the highest cytotoxic activity against MCF 7, A2780, and HT29 cancer cell lines with IC 50 values at 2.17 µM, 0.53 µM, and 2.16 µM, respectively, and was 2-9 folds more selective against tested cancer cell lines compared to the normal human fetal lung fibroblasts (MRC5). It also doubled MCF 7 apoptotic populations and caused G 1 cell cycle arrest. The acetylated compound 9 exhibited cytotoxic activity against MCF 7 and HT29 cancer cell lines with IC 50 values at 2.19 µM and 3.18 µM, respectively, and was 6-8 folds more cytotoxic to tested cancer cell lines compared to the MRC5 cells.

Suaeda vermiculata , a halophyte consumed by livestock, is also used by Bedouins to manage liver disorders. The aqueous-ethanolic extract of S. vermiculata , its subsequent fractions, and pure compounds, i.e ., pheophytin-A (1), isorhamnetin-3- O -rutinoside (2), and quercetin (3), were evaluated for their hepatoprotective efficacy. The male mice were daily fed with either silymarin, plant aq.-ethanolic extract, fractions, pure isolated compounds, or carboxyl methylcellulose (CMC) for 7 days ( n = 6/group, p.o .). On the day 7 th of the administrations, all, except the intact animal groups, were induced with hepatotoxicity using paracetamol (PCM, 300 mg/kg). The anesthetized animals were euthanized after 24 h; blood and liver tissues were collected and analysed. The serum aspartate transaminase (AST) and alanine transaminase (ALT) levels decreased significantly for all the S. vermiculata aq.-ethanolic extract, fraction, and compound-treated groups when equated with the PCM group ( p < 0.0001). The antioxidant, superoxide dismutase (SOD), increased significantly ( p < 0.05) for the silymarin-, n -hexane-, and quercetin-fed groups. Similarly, the catalase (CAT) enzyme level significantly increased for all the groups, except for the compound 2-treated group as compared to the CMC group. Also, the glutathione reductase (GR) levels were significantly increased for the n -butanol treated group than for the PCM group. The oxidative stress biomarkers, lipid peroxide (LP) and nitric oxide (NO), the inflammatory markers, IL-6 and TNF- α , and the kidney's functional biomarker parameters remained unchanged and did not differ significantly for the treated groups in comparison to the PCM-induced toxicity bearing animals. All the treated groups demonstrated significant decreases in cholesterol levels as compared to the PCM group, indicating hepatoprotective and antioxidant effects. The quercetin-treated group demonstrated significant improvement in triglyceride level. The S. vermiculata aq.-ethanolic extract, fractions, and the isolated compounds demonstrated their hepatoprotective and antioxidant effects, confirming the claimed traditional use of the herb as a liver protectant., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Salman A. A. Mohammed et al.)

Streptomyces smyrnaeus UKAQ&#95;23, isolated from the mangrove-sediment, collected from Jubail,Saudi Arabia, exhibited substantial antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), including non-MRSA Gram-positive test bacteria. The novel isolate, under laboratory-scale conditions, produced the highest yield (561.3 ± 0.3 mg/kg fermented agar) of antimicrobial compounds in modified ISP-4 agar at pH 6.5, temperature 35 °C, inoculum 5% v/w, agar 1.5% w/v, and an incubation period of 7 days. The two major compounds, K 1 and K 2 , were isolated from fermented medium and identified as Actinomycin X 2 and Actinomycin D, respectively, based on their structural analysis. The antimicrobial screening showed that Actinomycin X 2 had the highest antimicrobial activity compared to Actinomycin D, and the actinomycins-mixture (X 2 :D, 1:1, w/w) against MRSA and non-MRSA Gram-positive test bacteria, at 5 µg/disc concentrations. The MIC of Actinomycin X 2 ranged from 1.56-12.5 µg/ml for non-MRSA and 3.125-12.5 µg/ml for MRSA test bacteria. An in-silico molecular docking demonstrated isoleucyl tRNA synthetase as the most-favored antimicrobial protein target for both actinomycins, X 2 and D, while the penicillin-binding protein-1a, was the least-favorable target-protein. In conclusion, Streptomyces smyrnaeus UKAQ&#95;23 emerged as a promising source of Actinomycin X 2 with the potential to be scaled up for industrial production, which could benefit the pharmaceutical industry., (© 2021. The Author(s).)

Pulicaria jaubertii is a medicinal herb that alleviates inflammations and fever. Chromatographic separation, phytochemical characterization, and in vitro biological activities of the plant n -hexane extract were conducted for the first time in this study. Six compounds were isolated for the first time from the n -hexane fraction of Pulicaria jaubertii aerial parts and were identified on the bases of NMR and MS analyses as pseudo-taraxaterol ( 1 ), pseudo-taraxasterol acetate ( 2 ), 3β-acetoxytaraxaster-20-en-30-aldehyde ( 3 ), calenduladiol-3- O -palmitate ( 4 ), stigmasterol ( 5 ), and α-tocospiro B ( 6 ). Compound ( 6 ) was a rare tocopherol-related compound and was isolated for the first time from family Asteraceae, while compound ( 3 ) was isolated for the first time from genus Pulicaria . The total alcoholic extract and n -hexane fraction were tested for their anti-inflammatory, antidiabetic, and cytotoxic activities. The n -hexane fraction has dose dependent red blood cells (RBCs) membrane stabilization and inhibition of histamine release activities with IC 50 : 60.8 and 72.9 µg/mL, respectively. As antidiabetic activity, the alcoholic extract exerted the most inhibition on the activity of yeast α-glucosidase, with an IC 50 : 76.8 µg/mL. The n -hexane fraction showed cytotoxic activity against hepatocarcinoma (HepG-2), breast carcinoma (MCF-7), and prostate carcinoma (PC-3) cell lines with IC 50 : 51.8, 90.8 and 62.2 µg/mL, respectively. In conclusion, the anti-inflammatory effect of Pulicaria jaubertii might be attributed to the triterpenoid constituents of the n -hexane extract of the plant.

Background: Breaking bad news is an important task for doctors in different specialties. The aim of the study was to assess adherence of Sudanese doctors to the SPIKES protocol in breaking bad news., Methods: A descriptive cross-sectional study recruited 192 doctors, at Wad Medani teaching hospital, Sudan. A questionnaire-based on SPIKES protocol was distributed among 10 departments in our hospital. Data were analyzed using SPSS and Microsoft excel., Results: There were (n = 101, 52.6%) females and (n = 91, 47.4%) males among the participants. 95.3% have been involved in breaking bad news, but only 56.3 received education and training about this issue. 43% admitted bad experience in breaking bad news, while 65.6% mentioned that bad news should be delivered directly to patients. The majority (>90%) agreed training is needed in the area of breaking bad news. Usual adherence to the SPIKES protocol was reported in a range of 35-79%, sometimes adherence was reported in a range of 20-44% while never adherence was reported in a range of zero-13.5%. Consultants, registrars, obstetrician and gynecologists and surgeons achieved high scores in breaking bad news. Training is an important factor in achieving high score in SPIKES protocol. The unadjusted effect of background factors on SPIKES score, showed that only training has significant impact on protocol adherence (P = 0.034, unadjusted; and P = 0.038 adjusted)., Conclusion: Large number of Sudanese doctors will try to adhere to SPIKES protocol. Training is an important factor in the success of breaking bad news., Competing Interests: Conflict of interest: The authors claim no conflicts of interest., (© 2020 the Author(s), licensee AIMS Press.)

Background: Exposure to lead (Pb) has been associated with endocrine, hematological, gastrointestinal, renal and neurological problems in humans. However, effects on the thyroid gland are controversial., Objectives: The aim of the present study was to assess thyroid function in foundry workers occupationally exposed to Pb and the mechanism of oxidative-antioxidant imbalance., Methods: Thyroid function parameters and markers of oxidative stress were examined in 59 adult males who had been occupationally exposed to Pb. The results were then compared to those of 28 male subjects who had no history of Pb exposure or thyroid abnormalities and served as a control group., Results: Mean blood lead levels (16.5±1.74 μg/dl) were significantly higher among the exposed workers compared to those of the control group (12.8±1.16 μg/dl, (p <0.001)). The exposed group had significantly increased free triiodothyronine (FT3), free thyroxine (FT4) and significantly decreased thyroid stimulating hormone (TSH) (1.77±0.44 μIU/ml), whereas the control group had a TSH level of 2.61±0.94 μIU/ml (p< 0.0001). A state of oxidative stress was indicated by the significant increase in mean levels of malondialdehyde (MDA) and significant decrease in glutathione (GSH) (p < 0.0001). There was a significant positive correlation (r=0.358, p <0.05) between blood lead levels (BLL) and duration of employment, while BLL showed a significant negative correlation with TSH (r =-0.486, p <0.001), and GSH (r =-0.336, p <0.05). Of the occupationally exposed workers, 32.76% had elevated thyroid hormones. The results showed a significant positive relationship between GSH and TSH (β coefficient=0.274, p < 0.05), MDA with FT3 (β coefficient=0.355, p < 0.05) and FT4 (β coefficient = 0.491, p < 0.0001) among exposed workers., Conclusions: Workers exposed to Pb dust proved to be at risk for hyperthyroidism, which was found to have a significant role in oxidative-antioxidant imbalance present among workers with increasing duration of exposure., Participant Consent: Obtained., Ethics Approval: This study was approved by the Ethical Committee of the National Research Centre in Egypt (NRC) under the registration number 15225., Competing Interests: The authors declare no competing financial interests., (© Pure Earth 2020.)

Three previously undescribed oleanane-type triterpenoidal saponins named caspicaosides L-N were isolated from the fruits of Gleditsia caspica Desf. The aglycons of these saponins were echinocystic acid, erythrodiol and 12-oleanene-3,28,30-triol. Caspicaoside L is a bisdesmosidic saponin acylated with two monoterpenic acids. It has a disaccharide moiety made up of glucose and arabinose attached to C-3 and pentasaccharide moiety linked to C-28 made up of one glucose, 2 xyloses, one inner rhamnose and one terminal rhamnose which was acylated with two identical monoterpenic acids. Caspicaoside M is a monodesmosidic saponin with a trisaccharide moiety at C-3 made up of glucose, xylose and arabinose, while caspicaoside N has a disaccharide moiety at C-3 made up of glucose and arabinose. Their structures were determined by extensive 1D and 2D (DQF-COSY, HSQC, TOCSY, 1 H- 13 C-HSQC-TOCSY, HMBC, ROESY, NOESY) NMR, HRESIMS analyses and chemical degradation. The cytotoxicity MTT-based assay showed that caspicaosides M, N and L, respectively, exhibited high cytotoxic activity with IC 50  ≤ 10 μM (72 h) at least against one of the three used cancer cell lines, MCF 7, A2780 and HT 29; and were 2-34 folds selective against the normal fibroblasts (MRC 5). All compounds also induced apoptosis and caused G 2 /M arrest in MCF 7 cells (24 h); thus showing pro-apoptotic properties., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Many plants growing in Saudi Arabia are used in folk medicine for treatment of several diseases., Objective: Information of the chemical constituents and biological activities of plants is desirable for the discovery of therapeutic agents and discovering the actual value of folkloric remedies., Materials and Methods: The compounds were isolated and purified using silica gel column chromatography and preparative high-performance liquid chromatography-diode array detector (HPLC-DAD) Method. The alcoholic extracts of these plants were evaluated for biological activities., Results: Isolation and characterization of 1-feruloyl-β-D-glucopyranoside (1) as well as new secondary metabolite tryptophan methyl ester (2) were isolated for the 1(st) time from the Horwoodia dicksoniae. The three flavones were isolated from Rumex cyprius identified as isoorientin (3), vitexin (4), and Cynarosid (5). The structures of these compounds were characterized by nuclear magnetic resonance and mass spectrometry analysis and comparing with literature. The compounds were isolated and purified using silica gel column chromatography and preparative HPLC-DAD Method. The alcoholic extracts of these plants were evaluated for antimicrobial activities against two Gram-positive bacteria, two Gram-negative bacteria, and four pathogenic fungi. Both plants showed good activities against Syncephalastrum racemosum and Streptococcus pneumoniae with minimal inhibitory concentrations (MICs) 0.98 and 1.95 μg/mL, respectively. H. dicksoniae showed good activity against Aspergillus fumigates with an MIC 1.95 μg/mL. The two extracts showed also effective free radical scavenging activities in the 1,1-diphenyl-2-picrylhydrazyl assay. H. dicksoniae exhibited remarkable cytotoxic activity against Human breast cancer mammary cancer cells-7, Human liver cancer human hepatoma carcinoma cells-2, and human lung carcinoma (A-549) cell lines., Conclusions: It was suggested that further work should be carried out to isolate, purify, and characterize the active constituents responsible for the activity of these plants., Summary: New secondary metabolite Tryptophane methyl ester as well as 1-feruloyl-β-D-glucopyranoside were isolated for the first time from the HD.Isoorientin, vitexin and Cynarosid were isolated from RC.HD exhibited good activity against Aspergillus fumigates with an MIC 1.95 µg mL(-1).HD showed significant cytotoxic activity against Human breast cancer (MCF-7), Human liver cancer (HepG-2) and Human lung carcinoma (A-549) cell lines.

One new monoterpene glucoside and five dihydroflavonols were isolated for the first time from the aerial parts of Pulicaria jaubertii and identified as p-menthane-2-O-β-D-glucopyranoside [1], dihydroquercetin (taxifolin) [2], 7,3'-di-O-methyltaxifolin [3], 3'-O-methyltaxifolin [4], 7-O-methyltaxifolin (padmatin) [5] and 7-O-methyl-dihydrokampferol (7-O-methylaromadenderin) [6]. The structures of these compounds were unambiguously assigned on the basis of NMR spectroscopic data ((1)H, (13)C, DEPT, HSQC, HMBC) and MS analysis. 2D-NMR methods required revision of assignments of H-6 and H-8 for dihydroflavonol compounds. Possible cytotoxic activity as well as blood pressure (BP) lowering activity were tested. The alcoholic extract showed cytotoxic activity against prostate carcinoma (PC-3), breast carcinoma (MCF-7) and hepatocellular carcinoma (HepG-2) human cell lines with IC50 19.1, 20.0 and 24.1 μg, respectively. The higher dose levels of the alcoholic extract significantly reduced normal BP of rats in a dose-dependent manner.

Background: Isolation and structure elucidation of flavan-3-ol constituents from the leaves of Ficus spragueana and their cytotoxic activity., Materials and Methods: Different open silica gel column chromatographic techniques with different solvent systems were used for the separation of the constituents of the ethyl acetate-soluble fraction of the alcoholic extract of Ficus spragueana leaves. The structures of these compounds were assigned on the basis of spectroscopic analyses and comparison with literature data. MTT colorimetric assay method (Viability assay) was used for the evaluation of cytotoxic activity of compound 1 against human breast cancer (MCF-7) and human liver cancer (HepG2) cell lines., Results: The isolation of one flavan-3-ol dimer and was identified as (-)-afzelechin-(4α→8)-epicatechin 1, and two flavan-3-ol monomers and were identified as (-)-epiafzelechin 2 and (-)-epicatechin 3. Compound 1 was relatively inactive against human breast cancer (MCF-7) cell line at the tested concentrations as compared with the standard. However, at a concentration (50 ΅g) it was found to give inhibition upon the proliferation of examined human liver (HepG2) tumor cell line., Conclusions: Compound 1 is a new flavan-3-ol dimer and it showed a potent cytotoxic activity against human liver (HepG2) tumor cell line.

The versatile synthon (E)-2-((dimethyl amino)methylene)cyclooctanone (2) was used as a key intermediate for the synthesis of cyclooctanones and cyclooctane-based heterocycles with pyrazole, isoxazole, pyrimidine, pyrazolopyrimidine, triazolopyrimidine and imidazopyrimidine derivatives via its reactions with several nitrogen nucleophiles. The newly synthesized compounds were screened in vitro for their antimicrobial activity against pathogenic microorganisms (Listeria monocytogenes, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans). Most of the tested compounds showed moderate to high antibacterial and antifungal effects against the tested pathogenic microorganisms. Among the synthesized compounds, 2-((p-sulfonamidophenyl)methylene)cyclooctanone (5) showed excellent activity against Listeria monocytogenes., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A convenient synthesis of a series of thiosemicarbazide, 1,3,4-oxadiazole, 1,3,4-thiadiazole, thiazole, 1,2,4-triazole, pyrazole and dioxoisoindoline derivatives incorporating 1,2,4-triazolo[4,3-a]pyrimidine via the reaction of the readily accessible 1,5-dihydro-5-oxo-1.7-diphenyl-1,2.4-triazolo[4,3-a]pyrimidine-3-carbohydrazide (2) with the appropriate reagents is described. The newly synthesized compounds were found to possess antihypertensive and diuretic activities compared to captopril and furosemide as reference controls, respectively.

Reaction of benzosuberone 1 with dimethylformamide-dimethylacetal (DMF-DMA) gives 2-dimethylamino-methylenebenozosuberone 2 which in turn reacts with heterocyclic amines to furnish new heterocyclic ring systems 6-9. Moreover, enaminone 2 reacts with hydrazine hydrate and hydroxylamine hydrochloride to afford the corresponding benzo[6,7]cyclohepta[1,2-c]pyrazole (10) and benzo[6,7]cyclohepta[2,1-d]isoxazole (12), respectively. In addition, the reactions of enaminone 2 with active methylene compounds afforded benzo[6,7]cyclohepta[1,2-b]pyridines (13-18). The X-ray crystallographic analysis of compounds 6 and 16, were recorded. We demonstrated the ability of nine new synthesized compounds to inhibit Hepatitis C Virus (HCV) and Subacute Sclerosing Panencephalitis (SSPE) due to structural similarity between ribavirin and some of the newly synthesized compounds were they contain triazoles and its bioisosters. In addition, the ability of ten synthesized compounds to react with the biologically relevant reactive nitrogen species, peroxynitrite was investigated indirectly by measurement of their ability to inhibit ONOO(-)-induced tyrosine nitration. The antioxidant activity of these ten compounds was also studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

Treatment of 3-cyanoacetyl indole 1 with the diazonium salts of 3-phenyl-5-aminopyrazole and 2-aminobenzimidazole afforded the corresponding hydrazones 4 and 5. 3-Cyanoacetyl indole reacted with phenylisothiocyanate to give the corresponding thioacetanilide derivative 7. Treatment of 7 with hydrazonoyl chlorides afforded the corresponding 1,3,4-thiadiazole derivatives 8a-f and 9. Also, the thioacetanilide reacted with alpha-haloketones to afford thiophene derivatives 10a,b (tenidap analogues), or thiazolidin-4-one derivative 11. The newly synthesized compounds were found to possess potential anti-inflammatory and analgesic activities.