Synthesis and In Vitro Evaluation of Some Novel Benzofuran Derivatives as Potential Anti-HIV-1, Anticancer, and Antimicrobial Agents

Rida, Samia M.,EI-Hawash, Soad A.M.,Fahmy, Hesham T.Y.,Hazza, Aly A.,EI-Meligy, Mostafa M.M. The Pharmaceutical Society of Korea 2006 Archives of Pharmacal Research Vol.29 No.1

A novel series of 1-(1-benzofuran-2-yl-ethylidene)-4-substituted thiosemicarbazides (2a-d) along with some derived ring systems: substituted-2,3-dihydro-thiazoles(3a-c, 4a-f) and thiazolidin-4-ones(5a-d and 6a-d), were synthesized. In addition, cyanoacetic acid-(1-benzofuran-2-yl-ethylidene) hydrazide(7) was used to prepare another new series of compounds consisting of substituted pyridin-2(1H)-ones(8a-c); 2-thioxo-2,3-dihydro-thiazoles(9a-d) and 2-thioxo-2,3-dihydro-6H-thiazolo[4,5-d]pyrimidin-7-ones (10a-c, 11a-c). The absolute configuration of compound 5c was determined by X-ray crystallography. The compounds prepared were evaluated for their in vitro anti-HIV, anticancer, antibacterial, and antifungal activities. Among the tested compounds, compounds 5c and 9a produced a significant reduction ㅐ ㄹ the viral cytopathic effect (93.19% and 59.55%) at concentrations $>2.0{\times}10^{-4}\;M\;and\;2.5{\times}10^{-5}\;M$respectively. Compound 9a was confirmed to have moderate anti-HIV activity. Compounds 2a, 2d, and 5c showed mild antifungal activity. However, none of the tested compounds showed any significant anticancer activity.

Histopathological and genetic changes proved the anti‑cancer potential of free and nano‑capsulated sinapic acid

Doaa A. Badr,Mohamed E. Amer,Wagih M. Abd‑Elhay,Mohamed S. M. Nasr,Tamer M. M. Abuamara,Harbi Ali,Aly F. Mohamed,Maha A. Youssef,Nasser S. Awwad,Yi‑Hsu Ju,Ahmed E. Fazary 한국응용생명화학회 2019 Applied Biological Chemistry (Appl Biol Chem) Vol.62 No.5

Cancer is known to be a fierce disease that causes a large percentage of the deaths worldwide. The common cancer treatments; chemotherapy, radiotherapy and surgery are known for their severe side effects; therefore scientists are working on finding solutions to reduce these drawbacks. One of these treatment systems is the sustained released drugs formulations, these systems depend on the encapsulation of the chemotherapy within an emulsifying agent, in order to obtain a slow drug release of low doses over long time intervals. In this study, the anti-cancer effects of free and encapsulated sinapic acid was tested against lung (A549), and colon (CaCo2) cancer cell lines, along with normal fibroblast cells (HFB4) as a negative control. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed for IC50 evaluation, also cell cycle assay was performed to detect cell cycle arrest status and related anti-apoptotic and pro-apoptotic; Blc-2, BAX, and P53 gene profile fold changes post cellular treatment. Data recorded revealed that encapsulated SA showed a lower toxicity than the free form to both cell lines and also to the normal cells. The cell cycle analysis showed a cell cycle arrest at the G2/M phase post cell treatment with the free and encapsulated sinapic acid accompanied with up regulation of Bax and P53 and a down regulation of Blc-2 genes in both cell lines. The data suggest a promising anti-cancer and anti-proliferative potential of free and encapsulated sinapic acid. Also they show that the anti-cancer effect of free and encapsulated sinapic acid is quite close.

Secreted Phosphoprotein 1 Promoter Genetic Variants Are Associated with the Response to Pegylated Interferon α Plus Ribavirin Combination Therapy in Egyptian Patients with Chronic Hepatitis C Virus Infection

( Fahmy T Ali ),( Mohamed A M Ali ),( Mayada M A Elgizawy ),( Ahmed M Elsawy ) 대한소화기학회 2015 Gut and Liver Vol.9 No.4

Background/Aims: The T-helper 1 (TH1) immune reaction is essential for the eradication of hepatitis C virus (HCV) during pegylated interferon α (PEG-IFN-α)- and ribavirin (RBV)-based therapy in chronic HCV patients. Secreted phosphoprotein 1 (SPP1) was shown to be a crucial cytokine for the initiation of a TH1 immune response. We aimed to investigate whether SPP1 single nucleotide polymorphisms (SNPs) may influence sustained virological response (SVR) rates. Methods: Two SNPs in the promoter region of SPP1 at the .443 C>T and .1748 G>A loci were genotyped in 100 patients with chronic HCV genotype 4 infection using a TaqMan SNP genotyping assay. Results: Sixty-seven patients achieved a SVR, and 33 patients showed no SVR. Patients carrying the T/T genotype at the .443 locus showed a significantly higher SVR rate than those carrying the C/T or C/C genotype (83.67% vs 50.98%, p<0.001). At the .1748 locus, the SVR rate was significantly higher in patients with the G/G genotype than in those with the A/A genotype (88.89% vs 52.63%, p=0.028) and in patients with the G/A genotype than in those with the A/A genotype (85.29% vs 52.63%, p=0.001). Conclusions: SPP1 SNPs at .443 C>T and .1748 G>A loci may be useful markers for predicting the response to PEG-IFN-α-2b plus RBV therapy in Egyptian patients with chronic HCV genotype 4 infection. (Gut Liver 2015;9:516-524)

Association of a Provisional New emm Type Opacity Factor-Negative Group A Streptococci Strain ST4529 with Septicemia

R.R. Rantty,M. Eshaghi,A.M. Ali,F. Jamal,K. Yusoff The Microbiological Society of Korea 2001 The journal of microbiology Vol.39 No.3

Group A Streptococcus strain ST4529 is a provisional new ems type which has been recently reported in Malaysia (Jomal, et al. 1999. Energ. Infect . Dis. 5,10-14). This strain was found to be opacity factor (OF) negative with a Tl phenotype. Usually, OF negative strains with T1 phenotypes are associated with acute rheumatic fever. However, strain ST4529 was isolated from the blood of a patient with septicemia. Comparison of the deduced amino acid sequence of the mature hypervariable N-terminus of ST4529 showed only 43% identity with that of M5, the closest matched OF negative strain with a T1 phenotype. Thus, ST4529 most probably encodes a new serospecifically unique M protein which is associated with septicemia rather than pharyngitis infections. The strains with these phenotypes are very important because their sequences should be considered for developing any anti-streptococcal vaccines.

Preparation of superparamagnetic maghemite (γ-Fe2O3) nanoparticles by wet chemical route and investigation of their magnetic and dielectric properties

Kashif Ali,A.K. Sarfraz,Imran M. Mirza,A. Bahadur,S. Iqbal,A. ul Haq 한국물리학회 2015 Current Applied Physics Vol.15 No.8

Maghemite (γ-Fe2O3) nanoparticles have been synthesized using a wet chemical route, optimizing the reaction time, PH value and size of the crystallite during synthesis. The Powder X-ray diffraction (XRD) measurements confirmed the presence of an impurity free maghemite phase in our sample with an average crystallite size of 16 nm as calculated from the DebyeeScherrer equation. In physical characterization, the room temperature hysteresis (M-H loop) and blocking temperature (as observed from the M-T plot) revealed that the particles are in the superparamagnetic phase at room temperature. Dielectric behaviour of γ-Fe2O3 with respect to the variation of frequency and temperature was also performed. At room temperatures, we observe a decaying behaviour of both dielectric constant (έ) and tangent looses (tanδ) at smaller frequencies while at higher frequencies both saturate to smaller constant values. In temperature dependent dielectric properties we notice that the dielectric constant (both real and imaginary parts) show an increasing trend with increasing temperatures but an overall slower enhancement at elevated frequencies. The former effect can be attributed to the possible delocalization of impurities at higher temperatures while the latter effect can be explained as an inability of the electric dipole moments to respond at higher frequencies.

Distribution of Glutathione S-Transferase Omega Gene Polymorphism with Different Stages of HBV Infection Including Hepatocellular Carcinoma in the Egyptian Population

Shaban, Nadia Z,Salem, Halima H,Elsadany, Mohamed A,Ali, Bahy A,Hassona, Ehab M,Mogahed, Fayed AK Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4

Background: Infection with hepatitis B virus (HBV) is a major global public health problem, with a wide spectrum of clinical manifestations. Human cytosolic glutathione-S-transferases (GSTs) include several classes such as alpha (A), mu (M), pi (P), sigma (S), zeta (Z), omega (O) and theta (T). The present study aimed to investigate the role of GST omega genes (GSTO1 and GSTO2) in different groups of patients infected with HBV. Materials and Methods: HBV groups were classified according to clinical history, serological tests and histological analysis into normal carriers (N), acute (A), chronic (CH), cirrhosis (CI) and hepatocellular carcinoma (HCC) cases. The study focused on determination of the genotypes of GST omega genes (GSTO1 and GSTO2) and GST activity and liver function tests. Results: The results showed that GSTO1 (A/A) was decreased in N, A, CH, CI and HCC groups compared to the C-group, while, GSTO1 (C/A) and GSTO1(C/C) genotypes were increased significantly in N, A, CH, CI and HCC groups. GSTO2 (A/A) was decreased in all studied groups as compared to the C-group but GSTO2(A/G) and GSTO2(G/G) genotypes were increased significantly. In addition, GST activities, albumin and TP levels were decreased in all studied groups compared to the C-group, while the activities of transaminases were increased to differing degrees. Conclusions: The results indicate that GSTO genetic polymorphisms may be considered as biomarkers for determining and predicting the progression of HBV infection.

Reaction of Five Non-cereal Grasses to Five Races and Two Host Selective Toxins of Pyrenophora tritici-repentis

Ali, Shaukat,Langham, M.A.C. The Korean Society of Plant Pathology 2015 Plant Pathology Journal Vol.31 No.3

Alternative hosts increase the difficulty of disease management in crops because these alternate hosts provide additional sources of primary inoculum or refuges for diversity in the pathogen gene pool. Agropyron cristatum (crested wheatgrass), Bromus inermis (smooth bromegrass), Pascopyrum smithii (western wheatgrass), Stipa viridula (green needlegrass), and Thinopyrum intermedium (intermediate wheatgrass), commonly identified in range, prairie, verge, and soil reclamation habitats, serve as additional hosts for Pyrenophora tritici-repentis, the cause of tan spot in wheat (Triticum aestivum L.). A. cristatum (five lines), B. inermis (seven lines), P. smithii (four lines), S. viridula (two lines), and T. intermedium (six lines) were tested for their reactions to 30 representative P. tritici-repentis isolates from races 1-5. Plants were grown until the two-three-leaf stage in a greenhouse, inoculated individually with the 30 isolates, held at high humidity for 24 h, and rated after 7 days. All lines developed lesion types 1-2 (resistant) based on a 1-5 rating scale. Also, leaves from an additional plant set were infiltrated with two host selective toxins, Ptr ToxA as a pure preparation and Ptr ToxB as a dilute crude culture filtrate. All lines were insensitive to the toxins. Results indicate that these grass hosts have a limited or nonsignificant role in tan spot epidemiology on wheat in the northern Great Plains. Additionally, the resistant reactions demonstrated by the grass species in this research indicate the presence of resistance genes that can be valuable to wheat breeding programs for improving wheat resistance to P. tritici-repentis.

Highly selective fluorescent probe based on new coordinated cationic polyvinylpyrrolidone for hydrogen sulfide sensing in aqueous solution

Abd-Elaal, Ali A.,Tawfik, Salah M.,Lee, Yong-Ill Elsevier 2017 Journal of molecular liquids Vol.247 No.-

<P>A cationic polyvinylpyrrolidone derivative (Cat-PVP) was prepared via Claisen-Schmidt condensation in KOH media (1.0 mM) and characterized using FT-IR and H-1 NMR spectroscopy. The prepared Cat-PVP was utilized to prepare a stable fluorescent copper coordinate Cat-PVP with outstanding properties. The Cu-Cat-PVP was successfully used to detect hydrogen sulfide ( H2S) due to the strong affinity between sulfur and copper. The quenching effect on the fluorescence intensity of the Cu-Cat-PVP probe showed very good linearity with H2S concentrations in the range of 1-40 mu M, with a detection limit as low as 0.13 mu M. The promising probe displayed high selectivity toward H2S over anions and bio-thiols and was successfully applied for detecting H2S in real samples such as human serum and water. (C) 2017 Published by Elsevier B.V.</P>

The oncogenic phosphatase PPM1D confers cisplatin resistance in ovarian carcinoma cells by attenuating checkpoint kinase 1 and p53 activation

Ali, A Y,Abedini, M R,Tsang, B K Macmillan Publishers Limited 2012 Oncogene Vol.31 No.17

Cisplatin (CDDP: cis-diamminedichloroplatinum) resistance is a major hurdle in the treatment of human ovarian cancer (OVCA). A better understanding of the mechanisms of CDDP resistance can greatly improve therapeutic outcome for patients. A determinant of CDDP sensitivity in OVCA, p53, is activated by checkpoint kinase 1 (Chk1) in response to DNA damage. Although the oncogenic phosphatase protein phosphatase magnesium-dependent 1 (PPM1D) can deactivate both p53 and Chk1 through site-specific dephosphorylation, whether PPM1D has a role in CDDP resistance is unknown. Here, using pair-matched wild-type p53 CDDP-sensitive (OV2008) and -resistant (C13*) cells, and p53-compromised CDDP-resistant cells (A2780cp, OCC-1, OVCAR-3 and SKOV3), we have demonstrated (i) the existence of site-specific differences in phospho-Ser-Chk1 content between sensitive and resistant cells in response to CDDP; (ii) PPM1D, but not phosphoinositide-3-kinase-related kinase Ataxia Telangiectasia and Rad3 related protein (ATR), is important in the regulation of CDDP-induced Chk1 activation and OVCA cell chemosensitivity; (iii) PPM1D downregulation sensitizes resistant cells to CDDP primarily by activating Chk1 and p53. Our findings establish for the first time that PPM1D confers CDDP resistance in OVCA cells through attenuating CDDP-induced, Chk1-mediated, p53-dependent apoptosis. These findings extend the current knowledge on the molecular and cellular basis of cisplatin resistance and offer the rationale for PPMID as a potential target for treatment of chemoresistant OVCA.

Thiazolylazo 화합물의 분광학적, 자기적, 그리고 열적성질

Masoud, M.S.,Mohamed, G.B.,Abdul-Razek Y.H.,Ali A.E.,Khairy F.N. 대한화학회 2002 대한화학회지 Vol.46 No.2

Thiazolylazo 화합물과 barbituric산, uracil, thiouracil, citrazinic산 chromotrotropic산, gallict산, pyrogallol 그리고 salicylic산의 Co(II), Ni(II) 그리고 Cu(II) 착화합물의 제조하였고, $^1H$ NMR, IR, 그리고 전기 흡수 스펙트럼에 대한 pHdudgid에 의하여 규명하였다. 이온화형태, 전기적 전이 그리고 해리상수에 대하여 설명하였다. 구리 착화합물은 등방형 ESR스펙트럼이었으며 자기적으로 궤도 기여를 갖는 묽은 성질이었다. 상세한 DTA데이타를 얻었고, 그 결과를 토론하였다. The thiazolylazo compounds and their Co(II), Ni(II) and Cu(II) complexes of barbituric acid, uracil, thiouracil, citrazinic acid, chromotropic acid, gallic acid, pyrogallol and salicylic acid were pre-pared and characterized by $^1H$ NMR , IR and the effect of pH on the electronic absorption spectra . The mode of ionization, the electronic transitions and the dissociation constants were discussed. The stoichiometries of the complexes were of 1:1, 2:1 and 3:2 (M:L). The copper complexes are of isotropic ESR spectra (except that of gallic acid which showed a complicated one) and are of magnetically diluted behaviour with orbital con-tribution. Detailed DTA data were obtained and discussed.