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Accumulating evidence indicates that statins reduce the risk of different cancers and inhibit the proliferation of liver cancer cells. This study aims to explore whether the electrostatic conjugation of optimized fluvastatin (FLV) to human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) would enhance the anti-proliferative activity against HepG2 cells. FLV–TAT conjugation was optimized to achieve the lowest size with highest zeta potential. Nine formulae were constructed, using a factorial design with three factors—FLV concentration, TAT concentration, and pH of the medium—while the responses were zeta potential and size. The optimized formula showed a particle size of 199.24 nm and 29.14 mV zeta potential. Data indicates that conjugation of FLV to TAT (optimized formula) significantly enhances anti-proliferative activity and uptake by HepG2 cells when compared to raw FLV. Flow cytometry showed significant accumulation of cells in the pre-G phase, which highlights higher apoptotic activity. Annexin V staining indicated a significant increase in total cell death in early and late apoptosis. This was confirmed by significantly elevated caspase 3 in cells exposed to FLV–TAT preparation. In conclusion, the FLV–TAT optimized formula exhibited improved anti-proliferative action against HepG2. This is partially attributed to the enhanced apoptotic effects and cellular uptake of FLV.

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The phytochemical screening, antimicrobial and antitumor activities of ,, ,, , and determined. The best antibacterial activity; 41.8 ± 0.23 mm, 39.7 ± 0.25 mm, 35.8 ± 0.58 mm, 34.7 ± 0.51 mm and 32.7 ± 0.25 mm was obtained by against , against , against , against and against , respectively. While the highest antifungal activity; 35.9 ± 1.15 mm, 34.6 ± 0.34, 30.6 ± 0.26 mm and 29.9 ± 0.63 mm was obtained by against ,, and, respectively. The antitumor activity (IC) obtained by ; 3.1 ± 6.9 µg/ml, 14.3 ± 3.1 µg/ml and 22.7 ± 4.1 µg/ml was better than activity of vinblastine sulphate; 5.9 ± 0.4 µg/ml, 59.7 ± 2.1 µg/ml and 30.3 ± 1.4 µg/ml against breast carcinoma (MCF-7), cervical carcinoma (Hela) and colorectal carcinoma (CACO), respectively. alcoholic extract showed higher antitumor activity; 15.3 ± 5.3 µg/ml, 28.6 ± 3.6 µg/ml and 24.3 ± 4.1 µg/ml than vinblastine; 21.2 ± 0.9 µg/ml, 59.7 ± 2.1 µg/ml and 30.3 ± 1.4 µg/ml against prostate carcinoma (Pc3), cervical carcinoma (Hela) and colorectal carcinoma (CACO), respectively. Also, the antitumor activity of against cervical carcinoma (Hela) (37.1 ± 2.6 µg/ml) was potent than vinblastine sulphate (59.7 ± 2.1 µg/ml). The obtained results of LD and sub-chronic toxicity revealed that the plants have no toxicity.

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Background:The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging novel coronavirus responsible for the viral pneumonia outbreak (coronavirus disease-19 ) that has impacted millions of people, causing a tremendous global public health concern and number of fatalities. The development of novel antiviral agents is considered an urgent research subject. Objectives: The objective of the study is to discover the phenolic constituents of the methanolic extract of Tecoma mollis Humb. and Bonpl. heartwood and to investigate their potential inhibitory action against SARS-CoV-2 protease and/or entry proteins. Materials and Methods: The heartwood of T. mollis was extracted by maceration with 70% EtOH until complete exhaustion. The extract was concentrated under reduced pressure, mixed with distilled H 2 O and defatted with CHCl 3 to produce a CHCl 3 fraction, and then subjected to solvent fractionation with n-butanol to produce an n-butanol fraction. The n-butanol fraction was subjected to a silica gel column using CHCl 3 -MeOH gradient mixtures followed by reversed-phase high-performance liquid chromatography. The isolated compounds were identified using one-and two-dimensional nuclear magnetic resonance as well as mass spectroscopy. Molecular docking studies have been implemented to identify the binding pattern between ligands and target enzymes, i.e. main protease (M pro ) and spike protein receptor-binding domain (RBD), and compared with the currently used COVID-19 inhibitors. Molecular dynamic simulations have been performed to evaluate the dynamics and stability of proteinligand complexes. The obtained information is then correlated with the essential structural features, and finally the structure-activity relationship is suggested. Results: Fourteen phenolic glycosides were isolated from the methanolic extract of T. mollis Humb. and Bonpl. heartwood in addition to an iridoid, ixoside. The molecular docking study exhibited that the isolated compounds have a higher binding affinity toward the active site of M pro and the angiotensin-converting enzyme-2 binding site of spike protein RBD. The phenylpropanoids have higher inhibitory action with higher binding energy toward SARS-CoV-2 M pro protease as compared to spike protein RBD. Among all the isolated compounds, isoverbascoside (10) exhibited the most potent dual interaction with SARS-CoV-2 M pro protease and spike protein RBD with high binding energy of − 8.8 and − 7.2 kcal/mol, respectively. This showed better potency than the currently used M pro and spikeprotein inhibitors. Conclusion: Our study is the first report on the potential inhibitory action of phenylpropanoids for SARS-CoV-2 protease and spike protein. It also correlates between the reported antiviral activities of some isolated compounds with their potential inhibitory action for COVID-19 viral proteins. Our results on T. mollis extract constituents could help in the discovery of a promising repurposable drug candidate that could contribute to the development of an effective thera...

Essential oil composition of Plectranthus asirensis grown in Saudi Arabia was chemically analysed for the first time by various gas chromatography techniques (GC-MS, GC-FID, Co-GC, LRI determination and database and literature searches) using two different stationary phase columns (polar and nonpolar). This analysis led to the characterisation of a total of 124 components representing 98.5% of the total oil composition. The results revealed that P. asirensis oil was mainly dominated by monoterpenoids (90.7%) in which most representative constituents were thymol (66.0 ± 0.36%), γ-terpinene (14.0 ± 0.18%), p-cymene (5.2 ± 0.06%) and β-caryophyllene (3.0 ± 0.03%). It is worth mentioning here that this is the first report on the phytochemical constituents of P. asirensis.

A Micromonospora strain, isolate MT25T, was recovered from a sediment collected from the Challenger Deep of the Mariana Trench using a selective isolation procedure. The isolate produced two major metabolites, n-acetylglutaminyl glutamine amide and desferrioxamine B, the chemical structures of which were determined using 1D and 2D-NMR, including 1H-15N HSQC and 1H-15N HMBC 2D-NMR, as well as high resolution MS. A whole genome sequence of the strain showed the presence of ten natural product-biosynthetic gene clusters, including one responsible for the biosynthesis of desferrioxamine B. Whilst 16S rRNA gene sequence analyses showed that the isolate was most closely related to the type strain of Micromonospora chalcea, a whole genome sequence analysis revealed it to be most closely related to Micromonospora tulbaghiae 45142T. The two strains were distinguished using a combination of genomic and phenotypic features. Based on these data, it is proposed that strain MT25T (NCIMB 15245T, TISTR 2834T) be classified as Micromonospora provocatoris sp. nov. Analysis of the genome sequence of strain MT25T (genome size 6.1 Mbp) revealed genes predicted to responsible for its adaptation to extreme environmental conditions that prevail in deep-sea sediments.