Exploitation of Sugarcane Bagasse and Environmentally Sustainable Production, Purification, Characterization, and Application of Lovastatin by Aspergillus terreus AUMC 15760 under Solid-State Conditions.

Using the internal transcribed spacer (ITS) region for identification, three strains of Aspergillus terreus were identified and designated AUMC 15760, AUMC 15762, and AUMC 15763 for the Assiut University Mycological Centre culture collection. The ability of the three strains to manufacture lovastatin in solid-state fermentation (SSF) using wheat bran was assessed using gas chromatography-mass spectroscopy (GC-MS). The most potent strain was strain AUMC 15760, which was chosen to ferment nine types of lignocellulosic waste (barley bran, bean hay, date palm leaves, flax seeds, orange peels, rice straw, soy bean, sugarcane bagasse, and wheat bran), with sugarcane bagasse turning out to be the best substrate. After 10 days at pH 6.0 at 25 °C using sodium nitrate as the nitrogen source and a moisture content of 70%, the lovastatin output reached its maximum quantity (18.2 mg/g substrate). The medication was produced in lactone form as a white powder in its purest form using column chromatography. In-depth spectroscopy examination, including 1H, 13C-NMR, HR-ESI-MS, optical density, and LC-MS/MS analysis, as well as a comparison of the physical and spectroscopic data with published data, were used to identify the medication. At an IC50 of 69.536 ± 5.73 µM, the purified lovastatin displayed DPPH activity. Staphylococcus aureus and Staphylococcus epidermidis had MICs of 1.25 mg/mL, whereas Candida albicans and Candida glabrata had MICs of 2.5 mg/mL and 5.0 mg/mL, respectively, against pure lovastatin. As a component of sustainable development, this study offers a green (environmentally friendly) method for using sugarcane bagasse waste to produce valuable chemicals and value-added commodities.

Diterpenes and sterols from the Red Sea soft coral Sarcophyton trocheliophorum and their cytotoxicity and anti-leishmanial activities.

The ethyl acetate and dichloromethane-soluble fractions, from a soft coral Sarcophyton trocheliophorum total methanolic extract, exhibited significant anti-leishmanial and cytotoxic activities. These active fractions yielded a new cembranoid diterpene (1), two known analogues [sarcotrocheliol (2) and sarcophine (3)], and two sterols [(24S)-24-methylcholesterol (4) and gorgosterol (5)]. The structure of the new diterpene (1) was determined via a detailed analysis of its spectroscopic data. Compounds 3 and 5 demonstrated noticeable cytotoxicity on A549 (IC50 17.4 ± 1.9 µg/ml) and HepG2 (IC50 17.7 ± 1.5 µg/ml) cell lines, respectively. None of the isolates 1‒5 showed detectable anti-leishmanial activity (IC50 >100 µg/ml).

A Comprehensive In Silico Study of New Metabolites from Heteroxenia fuscescens with SARS-CoV-2 Inhibitory Activity.

Chemical investigation of the total extract of the Egyptian soft coral Heteroxenia fuscescens, led to the isolation of eight compounds, including two new metabolites, sesquiterpene fusceterpene A (1) and a sterol fuscesterol A (4), along with six known compounds. The structures of 1-8 were elucidated via intensive studies of their 1D, 2D-NMR, and HR-MS analyses, as well as a comparison of their spectral data with those mentioned in the literature. Subsequent comprehensive in-silico-based investigations against almost all viral proteins, including those of the new variants, e.g., Omicron, revealed the most probable target for these isolated compounds, which was found to be Mpro. Additionally, the dynamic modes of interaction of the putatively active compounds were highlighted, depending on 50-ns-long MDS. In conclusion, the structural information provided in the current investigation highlights the antiviral potential of H. fuscescens metabolites with 3ß,5α,6ß-trihydroxy steroids with different nuclei against SARS-CoV-2, including newly widespread variants.

Antimicrobial activities of Diltiazem Hydrochloride: drug repurposing approach.

Background: The growing concern of antibiotic-resistant microbial strains worldwide has prompted the need for alternative methods to combat microbial resistance. Biofilm formation poses a significant challenge to antibiotic efficiency due to the difficulty of penetrating antibiotics through the sticky microbial aggregates. Drug repurposing is an innovative technique that aims to expand the use of non-antibiotic medications to address this issue. The primary objective of this study was to evaluate the antimicrobial properties of Diltiazem HCl, a 1,5-benzothiazepine Ca2 + channel blocker commonly used as an antihypertensive agent, against four pathogenic bacteria and three pathogenic yeasts, as well as its antiviral activity against the Coxsackie B4 virus (CoxB4). Methods: To assess the antifungal and antibacterial activities of Diltiazem HCl, the well diffusion method was employed, while crystal violet staining was used to determine the anti-biofilm activity. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay was utilized to evaluate the antiviral activity of Diltiazem HCl against the CoxB4 virus. Results: This study revealed that Diltiazem HCl exhibited noticeable antimicrobial properties against Gram-positive bacteria, demonstrating the highest inhibition of Staphylococcus epidermidis, followed by Staphylococcus aureus. It effectively reduced the formation of biofilms by 95.1% and 90.7% for S. epidermidis, and S. aureus, respectively. Additionally, the antiviral activity of Diltiazem HCl was found to be potent against the CoxB4 virus, with an IC50 of 35.8 ± 0.54 µg mL-1 compared to the reference antiviral Acyclovir (IC50 42.71 ± 0.43 µg mL-1). Conclusion: This study suggests that Diltiazem HCl, in addition to its antihypertensive effect, may also be a potential treatment option for infections caused by Gram-positive bacteria and the CoxB4 viruses, providing an additional off-target effect for Diltiazem HCl.

Antileishmanial and lung adenocarcinoma cell toxicity of Withania somnifera (Linn.) dunal root and fruit extracts.

This study aims to evaluate the anti-Leishmania major and the lung adenocarcinoma (A549) cytotoxicity of Withania somnifera root and fruit. The total extracts were obtained by homogenisation in aqueous MeOH, and the sub-extracts [n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH), and methanol (MeOH)] were obtained by flash chromatography. The activity evaluation showed that n-BuOH sub-extracts from root and fruit exhibited noticeable antileishmanial promastigote properties. The n-hexane and EtOAc sub-extracts from both organs, and the MeOH sub-extract from the fruit exerted mild to moderate effects on the promastigotes. In-vitro growth-inhibitory test results on axenic amastigote and cytotoxicity testing on macrophages (RAW264.7), the parasite-host at the amastigote stage, revealed that the activity was mainly concentrated in the root EtOAc and n-BuOH sub-extracts and to a lesser extent the fruit MeOH and EtOAc, and the root n-hexane sub-extracts. Only the roots' EtOAc and n-BuOH sub-extracts demonstrated low cytotoxicity on the A549 cell line.

Ellagitannins and simple phenolics from the halophytic plant Tamarix nilotica.

Three new [nilotinins M8‒M10 (1‒3)] and two known [tamarixinin A (4) and gemin D (5)] ellagitannins and seven simple phenolics [gallic acid (6), methyl gallate (7), 3,4-di-O-methylgallic acid (8), ellagic acid (9), 3-O-methylellagic acid (10), methyl ferulate 3-O-sulphate (11), and 7,4'-di-O-methylkaempferol (12)] were isolated from the halophytic plant Tamarix nilotica (Ehrenb.) Bunge (Tamaricaceae). Their structures were determined based on intensive spectroscopic studies and comparisons with reported data. Compounds 4, and 6-8 were evaluated for their cytotoxicity against lung adenocarcinoma cell line (A549) and anti-leishmanial activity against Leishmania major. Compounds 4, 6 and 7 showed promising cytotoxic properties against A549 (IC50 29 ± 2.3, 10.5 ± 0.7, and 20.7 ± 1.9 µg/mL), while compounds 4 and 7 showed higher growth-inhibitory effects against L. major promastigotes (IC50 40.5 ± 2.7 and 38.4 ± 2.5 µg/mL), as compared with the standards doxorubicin (IC50 0.42 µg/mL) and miltefosine (IC50 9.43 µg/mL), respectively.

Cytotoxicity and chemical profiling of the Red Sea soft corals Litophyton arboreum.

The objective of this research was to evaluate the cytotoxic activities of the fractions and isolated compounds of the soft corals Litophyton arboreum against A549, MCF-7 and HepG2 cell lines by MTT assay method, and to chemically investigate the various metabolites of its total extract using LC-HR-ESI-MS metabolomic profiling. The metabolomic profiling revealed the presence of various metabolites, mainly sesquiterpenes and steroids reported for the first time in L. arboreum. Additionally, eight compounds (1-8) have been isolated from the n-hexane-chloroform (1:1) fraction that exhibited noticeable activity towards A549, MCF-7 and HepG2 cell lines. The steroids (5 and 6), and the sesquiterpene (1) exerted noticeable activity against A549 cell line (IC50 28.5 ± 4.4, 36.9 ± 2.9 and 67.3 ± 9.9 µM/mL, respectively) compared to etoposide as standard cytotoxic agent (IC50 48.3 ± 7.6 µM/mL). Compound 6 also exhibited cytotoxicity against MCF-7 cell line (IC50 55.3 ± 4.9 µM/mL).

The Antioxidant and Antitumor Efficiency of Litophyton sp. Extract in DMH-Induced Colon Cancer in Male Rats.

One of the most common tumors to cause death worldwide is colon cancer. This study aims to investigate the antitumor potency of Litophyton sp. methanolic extract (LME) against DMH-induced colon cancer in adult male rats. Group (1) normal rats served as the control, group (2) normal rats were ip-injected with LME at a dose of 100 µg/kg/day, group (3) DMH-induced colon cancer animals, and group (4) colon cancer-modeled animals were treated with LME (100 µg/kg/day) for six weeks. The results revealed that injection of LME markedly regenerated the colon cancer pathophysiological disorders; this was monitored from the significant reduction in the values of serum biomarkers (CEA, CA19.9, AFP), cytokines (TNF-α and IL1ß), and biochemical measurements (ALAT, ASAT, urea, creatinine, cholesterol, and triglycerides) matched significant increase of apoptotic biomarkers (CD4+); similarly, colon DNA fragmentation, MDA, and NO levels were down-regulated. In contrast, a remarkable upregulation in colon SOD, GPx, GSH, and CAT levels was noted. Moreover, the colon histopathological architecture showed obvious regenerations. Chromatography of LME resulted in the purification of two polyhydroxylated steroids (1 and 2) with potential cytotoxic activities. LME performed therapeutic potential colon tumorigenesis; therefore, LME may have a promising chemo-preventive feature against colon cancer, probably via enhancement of the apoptosis pathway, improvement of the immune response, reduction of inflammation, or/and restoration of the impaired oxidative stress.

Cytotoxic polyhydroxy sterols from the Egyptian Red Sea soft coral Sarcophyton acutum.

The methanolic extract and its sub-extracts (viz, n-hexane, DCM, EtOAc and MeOH) of the soft coral Sarcophyton acutum were evaluated as anti-Leishmania major and as anticancer (against the HepG2, MCF-7, and A549 cell lines) using the MTT assay. Six polyhydroxy sterols (1-6) were isolated from the most active cytotoxic and anti-leishmanial EtOAc-soluble fraction. Their structures were established as two new polyhydroxy sterols, acutumosterols A (1) and B (2), and four known structural analogues (3-6) by intensive spectroscopic analyses, and by comparison with data of related compounds. Compound 4 exerted noticeable cytotoxicity against HepG2 cell line (IC50 17.2 ± 1.5 µg/mL), while the other pure isolates showed weak to moderate cytotoxicity (24.8 ± 2.8-57.2 ± 5.2). The results were discussed in relation to the structural features of these closely related sterols.