Phytochemical and antimicrobial investigation of the leaves of five Egyptian mango cultivars and evaluation of their essential oils as preservatives materials.

The sterols, hydrocarbons and fatty acids constituents of the leaves of five mango cultivars locally implanted in Egypt were identified. The effect of their essential oils (EOs) against food borne microorganisms was studied as preservative materials. The chemical constituents of the EOs isolated from mango leaves were identified by Gas Chromatography-Mass spectrometry (GC-MS) technique. Trans-caryophyllene, α-humulene and α-elemene were identified as terpene hydrocarbons, while 4-hydroxy-4-methyl-2-pentanone as oxygenated compounds were recorded in all tested cultivars with variable amounts. Results showed that Staphylococcus aureus and Escherichia coli were the most sensitive microorganisms tested for Alphonso EOs. On the other hand, Salmonella typhimrium was found to be less susceptible to the EOs of the studied cultivars. The EOs of different mango cultivars induced a steady decrease in the activity of amylase, protease and lipase at the minimum inhibitory concentration (MIC). The treatment of the tested bacteria with the EOs of mango cultivars caused a steady loss in enterotoxins even when applied at the sub-MIC. Bacteria-inoculated apple juice treated with minimum bactericidal concentration of Alphonso oil was free from the bacteria after 5 days of incubation at 25 °C. Eighteeen volatile compounds were found to reduce the activity of the amylase enzyme and the most active was cedrelanol (-7.6 kcal mol-1) followed by alpha-eudesmol (-7.3 kcal mol-1) and humulene oxide (-7 kcal mol-1). The binding mode of both of cedrelanol and alpha-eudesmol with amylase enzyme was illustrated.

Development, synthesis, and biological evaluation of sulfonyl-α-l-amino acids as potential anti-Helicobacter pylori and IMPDH inhibitors.

Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes a crucial step in the biosynthesis of DNA and RNA, and it has been exploited as a promising target for antimicrobial therapy. The present study discusses the development and synthesis of a series of sulfonyl-α-l-amino acids coupled with the anisamide scaffold and evaluates their activities as anti-Helicobacter pylori and IMPDH inhibitors. Twenty derivatives were synthesized and their structures were established by high-resolution mass spectrometry and 1 H and 13 C nuclear magnetic resonance measurements. Four compounds (6, 10, 11, and 21) were found to be the most potent and selective molecules in the series with minimum inhibitory concentration (MIC) values <17 µM, which were selected to test their inhibitory activities against HpIMPDH and human (h)IMPDH2 enzymes. In all tests, amoxicillin and clarithromycin were used as reference drugs. Compounds 6 and 10 were found to have a promising activity against the HpIMPDH enzyme, with IC50 = 2.42 and 2.56 µM, respectively. Moreover, the four compounds were found to be less active and safer against hIMPDH2 than the reference drugs, with IC50 > 17.17 µM, which makes sure that their selectivity is toward HpIMPDH and reverse to that of amoxicillin and clarithromycin. Also, the synergistic antibacterial activity of compounds 6, 10, amoxicillin, and clarithromycin was investigated in vitro. The combination of amoxicillin/compound 6 (2:1 by weight) exhibited a significant antibacterial activity against H. pylori, with MIC = 0.12 µg/ml. The molecular docking study and ADMET analysis of the most active compounds were used to elucidate the mode-of-action mechanism.

Configuration and molecular structure of 5-chloro-N-(4-sulfamoylbenzyl) salicylamide derivatives.

A systematic study on sulfonamide derivatives with salicylamide core is presented for possible use in pharmaceutical applications. The molecular structure of eight different compounds has been investigated by FTIR in the frequency range 4000-400 cm-1 to recognize the possible geometrical shape of the molecules needed to uniquely identify the activity of molecule in cancer cell. The electronic charge distribution of these different compounds is further illustrated by UV-Vis spectroscopy in the frequency range 190-1100 nm. The theoretical results obtained from molecular modeling calculations showed that the hydrogen bonds between the OH, CO, NH, and/or CH groups vary from one compound to the other regarding their number and bond length. This confirms the experimental FTIR results regarding the position and broadening of the OH and NH groups due to free rotation of the amide group because of changing the compounds structure by adding different groups to the last phenyl ring. The hydrogen bonds take different directions and values from one compound to the other, which seems to be the most important factor regarding the activity of these different compounds in cancer cell. Both theoretical molecular modeling calculations and FTIR experimental results have strongly evaluated the relation between the chemical structure of 5-chloro-N (4-sulfamoylbenzyl) salicylamide derivatives and their biological activities.

Synthesis and biological evaluation of novel 5-chloro-N-(4-sulfamoylbenzyl) salicylamide derivatives as tubulin polymerization inhibitors.

A novel series of sulfonamide derivatives, coupled with a salicylamide scaffold, was designed and synthesized. The structures of the synthesized compounds were established using 1H NMR, 13C NMR and high-resolution mass spectroscopy. The synthesized compounds were tested in vitro against five types of human cell lines. Two were breast adenocarcinoma, including the hormone-dependent MCF-7 and the hormone-independent MDA-MB-231. The others were the colorectal adenocarcinoma Caco-2, the carcinoma HCT-116 and the immortalized retinal-pigmented epithelium, hTERT-RPE1. Nine sulfonamides were able to inhibit the growth of the four tested cancer cells. Compound 33 was the most active against the selected colon cancer (Caco-2 and HCT-116) subtypes, while compound 24 showed the best efficacy against the examined breast cancer (MCF-7 and MDA-MB-231) cells. The selectivity index introduced compounds 24 and 33 as having the best selectivity among the breast and colon subtypes, respectively. In vitro tubulin polymerization experiments and flow cytometric assays showed that compounds 24 and 33 led to cell cycle arrest at the G2/M phase in a dose-dependent manner by effectively inhibiting tubulin polymerization. Furthermore, the results of the molecular docking studies indicate that this class of compounds can bind to the colchicine-binding site of tubulin.

Structure and absolute configuration of some 5-chloro-2-methoxy-N-phenylbenzamide derivatives.

The absolute configuration of 5-chloro-2-methoxy-N-phenylbenzamide single crystal [compound (1)] and the effect of introducing -[CH2]n-, n=1,2 group adjacent to the amide group [compounds (2) and (3)], were studied. Furthermore, the replacement of the methoxy group with a hydroxy group [compound (4)] was defined. Proton and carbon-13 NMR spectrometer were used to record the structural information of the prepared compounds. X-ray single crystal diffractometer were used to elucidate the 3D structural configurations. Intensity data for the studied compounds were collected at room temperature. The X-ray data prove that compound (1) is almost planar, with maximum r.m.s. deviations of 0.210(3)Å corresponds to C13. This planarity starts to disturb by adding -[CH2]n-, n=1,2 groups between the NH group and the phenyl ring in compounds (2) and (3), respectively. By replacing the OCH3 group by an OH group in compound (4), the plane of the chlorophenyl moiety is nearly perpendicular to that of the phenyl ring. Such new structural configurations were further illustrated by the infrared, and ultraviolet-visible spectroscopy measurements in the frequency range 400-4000cm-1 and 190-1100nm, respectively. Spectroscopic analyses were verified with the help of molecular modeling using density functional theory. The estimated total dipole moment for the prepared compounds reflects its ability to interact with its surrounding molecules. The higher dipole moment for a given structures is combined with the higher reactivity for potential use in medicinal applications.