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Curcumin is a natural compound with numerous biological activities and a precursor for many drugs. Development of a convenient one pot synthetic method for synthesizing curcumin-based diazepines and diazoles having antibacterial activities is focussed in this study. A one pot condensation process was developed for synthesizing a novel class of curcumin-based diazoles and diazepines by reacting curcumin with 2-diamino compounds and hydrazines in presence of sulfuric acid as catalyst. IR and 1H NMR were used to characterize the molecular composition of the synthesized curcumin derivatives. The synthesized derivatives were tested for their in vitro antibacterial efficacy against Gram-negative and Gram-positive bacteria. The MIC concentrations ranged from 1.56 to 200 μg/mL. Ampicillin exhibited synergistic effects with compounds C1, C3, C4 and C8. In the genotoxicity test, compound C3 was found to have no effect on the DNA molecules of E. coli strains, suggesting that it is not mutagenic and/or genotoxic. Compound C2 had the strongest interaction with the investigated protein receptor sites when blind molecular docking was conducted on all compounds. Since both H-donating and H-accepting sites of this molecule interact efficiently during the docking. In addition, absorption, distribution, metabolism and excretion (ADME) study showed that compound C2 do not contradict the Lipinski’s rule of drug likeness and showed a low level of passive human gastrointestinal absorption. The results indicated that C2 could be most promising among the studied compounds.

Developing a new effective anticancer agent becomes an urgent need to overcome of current drug-resistance. In this study we demonstrated that curcumin with heterocyclic moiety can function as an anticancer agent in a human. A new series of curcumin-based benzodiazepines, diazepines and diazoles were prepared using a simple one pot process. The process involved a condensation reaction of curcumin with various 1,2 diamino compounds and hydrazine. The structures of the prepared heterocycles were identified by the spectroscopic methods FT-IR, 1H NMR, and 13C NMR. The in vitro anticancer activities of the synthesized curcumin-based heterocycles against HeLa cancer cells were evaluated by the 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The viability of HeLa cells was reduced in the range of 4.48- 14.57% within the studied concentrations. Curcumin-based diazepine 6 showed the highest cytotoxic effect on the HeLa cells at all concentrations. it reduced the viability of the tested HeLa cells in range of 4.48 % for the 400 μg /ml concentration to 4.95% for the 12.5 μg /ml concentration. Moreover, heterocyclic 6 showed the highest cytotoxic and cytostatic effect among the tested heterocyclics against Hela cells. It exhibited IC50 and a cytostatic effect of of 0.4572 and 0.08515 µg/ml, respectively at a nontoxic level, as the control L6 cells showed cytotoxic and cytostatic effect with IC50 values of 22.47 and 1.977 µg/ml, respectively. This study revealed that, the prepared curcumin-based compounds exhibit a promising anticancer activity against HeLa cancer cells at a nontoxic concentration.

Camel milk is an important nutritional source that historically been used in the treatment of cancer. Therefore, the main aim of the present study is to determine the in vitro anticancer effect of both camel milk and whey against cervix cancer (HeLa) cells. To perform that, skimmed milk as well as whey immunoglobulins concentrate samples were prepared at different concentrations (0, 1, 2.5, 5, 7.5 and 10 mg/ml). Then, the in vitro effect of the prepared concentrations on HeLa cells morphology and growth was investigated by tissue culture technique. Moreover, the anticancer activity of camel milk and whey against HeLa cells was estimated by the 3-[4, 5-dimethylthiazole-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. The obtained results displayed that both camel milk and whey reduced the viability of HeLa cells specially at 7.5 and 10 mg/ml. In addition, the viability of treated HeLa cells reduced after addition of both camel milk and whey to approximately 15% in a concentration dependent manner. In conclusion, this study showed the in vitro cytotoxic effect of camel milk and whey as they inhibited the growth of HeLa cells. Asian J. Med. Biol. Res. June 2019, 5(3): 231-236

Two new hydrated monocationic Cu(II) complexes with 1,3-propylenediamine and 1,2-ethylenediamine of general formula [CuBr(N-N)2·H2O]Br were prepared. The complexes were identified by means of several spectroscopic tools (Uv-visible, IR and MS), thermally (TG/DTA) and CHN-elemental analysis. The three dimensional structure for complex A and B was provide by X-ray diffraction studies and showed the Cu(II) ion as 4 + 1 + 1 coordinated, four nitrogen atoms of the diamine ligands, one bromide ion and one H2O semi-coordinated to the Cu(II) center, a typical trans effect is clearly observed in the two complexes. The molecular crystal structures are linked via several H-bonds like N_H…Br and N_H…O. Additionally, intra-molecular H-bonds of kind C_H…Br is observed; these interactions lead to crystal structure three dimensional architecture packing. Hirshfeld surfaces (HSA) analysis was served to figure out the inter-contacts and fingerprints atoms percentage. DNA-binding, antitumor and antibacterial effectiveness of the desired complexes were evaluated.

Two dicationic water soluble mixed triamine/diamine copper (II) complexes, of general formula [Cu(dien)NN]Br2(1–2) [dien = diethelenetriamine and NN is en = ethylenediamine or Me4en = N,N′,N,N′-tetramethylethylenediamine] were prepared under ultrasonic mode with a relatively high yield. These complexes were characterized by elemental microanalysis, UV visible IR spectroscopy, and thermal and electrochemical techniques. In addition, complex 2 structure was solved by X-ray single crystal and Hirshfeld surface analysis. The complex exhibits a distorted square pyramidal coordination environment around Cu(II) centre. The solvatochromism of the desired complexes was investigated in water and other suitable organic solvents. The results show that the Guttmann’s DN parameter values of the solvents have mainly contributed to the shift of the d–d absorption band towards the linear increase in the wavelength of the absorption maxima of the complexes. The complex 1 showed higher antibacterial activity against the studied microorganisms compared to complex 2. Both complexes revealed promising antibacterial activities., The authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for its funding of this Research group NO (RG-0257-1435-1436).

Under mode of ultrasonic vibration, the neutral octahedral mononuclear [trans-CuBr2(N ∩ N)2]·3H2O complex with N ∩ N = 2,2-dimethylpropane-1,3-diamine was obtained. The structure of the desired complex was characterized by UV–Vis. spectroscopy, FT-IR, EDX, MS, SEM, TG/DTA and CHN-analysis. The octahedral-structure of the desired Cu(II) complex was proven via XRD single-crystal diffraction and its molecular interactions were computed by Hirschfeld surface analysis. Alcohol (as solvent) and short ultrasonic vibration dose period played a critical role in sonochemistry synthesis of octahedral neutral trans-CuBr2(N ∩ N)2 complex instead of trigonal bi-pyramidal monocation [CuBr(N ∩ N)2]Br one. Due to the Jahn-Teller effect, the complex exhibited a trans bonds elongation along Br-Cu-Br axis originating a distorted-octahedral Cu(II), as revealed by the XRD measurements (Br-Cu = 3.04 A). Therefore, the Solvatochromic behavior of the complex was successfully performed since the trans di-bromide ions are loosely coordinated to Cu(II) center, the change in complex solutions colors by using different solvents which can be detected even by naked-eye supported atypical Jahn-Teller elongation effect formation. TG/DTA and Flynn Wall Ozawa (FWO) isoconversional kinetic methods were applied for the complex to figure out the thermal behavior, kinetic of the ligands de-structured and estimate its Ea/α relation. The complex binding mode to the CT-DNA was examined by UV–vis. spectroscopic, melting curve, CV and viscosity tests. The complex exhibited very strong DNA binding via an intercalation mode of coordination with Kb = 6.5 × 105 value.

Under mode of ultrasonic vibration, the neutral octahedral mononuclear [trans-CuBr

Two new hydrated monocationic Cu(II) complexes with 1,3-propylenediamine and 1,2-ethylenediamine of general formula [CuBr(N-N)

Two new mixed-ligand copper(II) complexes, [Cu(dipn)(N N)]Br2 (1–2) [dipn = dipropylenetriamine, N N = ethylenediamine (en) (1) and propylenediamine (pn) (2)], have been synthesized. These complexes were characterized by spectroscopic and thermal techniques. Crystal structure for 2 shows a distorted trigonal–bipyramidal geometry around Cu(II) ion with one solvate water molecule. Antimicrobial and antiproliferative assays were conducted to evaluate the biological activities of these complexes. The complexes exhibit a promising antimicrobial effect against an array of microbes at 200 μg/mL concentration. The antiproliferative assay shows a high potential of these complexes to target Human keratinocyte cell line with IC50 values of 155 and 152 μM. The absorption spectrum of 2 in water was modeled by time-dependent density functional theory (TD-DFT).

Fullerenes are a class of nanomaterials with unique electronic properties that can be harnessed for use in various applications. We have found their biologic function critically depends on the structure of the side chain moieties added to the core carbon cage. A therapeutic candidate termed C70-Tetraglutamate (TGA), previously shown to have potent anti-inflammatory properties, was selected to determine the molecular interactions in human serum and in resting or FceRI-activated human mast cells (MC). The identity of TGAbinding molecules was analyzed using NanoLC-MS/MS peptide sequencing technology. We found that TGA predominately bound to alpha-2-macroglobulin precursor, Serpin peptidase inhibitor, and serum albumin in human serum. In non-activated MC, TGA interacted predominantly with aminopeptidase N precursor, dipeptidyl peptidase 4, and human fibroblast activation. In MC activated through FceRI, predominant interactions were observed between TGA and annexin A5, superoxide dismutase, and lysosomal membrane glycoprotein. These studies for the first time identify serum and cellular substrates of a fullerene-based anti-inflammatory compound which serves as a starting point for determining the mechanism of action of this therapeutic candidate.

RNA interference is an attractive strategy to fight against viral diseases by targeting the mRNA of viral genes. Most studies have reported the transient delivery of small interfering RNA or small hairpin (shRNA) expression constructs. Here, we present the production of transgenic mice stably expressing shRNA or miRNA targeting the IE180 mRNA (immediate early gene) of the pseudorabies virus (PRV) which infects mice and farm animals. We firstly designed non-retroviral shRNA or miRNA expression vectors. Secondly, we selected the most efficient shRNA construct that targeted either the 5'part or 3'UTR of the IE mRNA and was able to knockdown the target gene expression in cultured cells, by measuring systematically the shRNA content and comparing this with the interfering effects. We then produced four lines of transgenic mice expressing different amounts of shRNA or miRNA in the brain but without signs of stimulation of innate immunity. Lastly, we tested their resistance to PRV infection. In all transgenic lines, we observed a significant resistance to viral challenge, the best being achieved with the shRNA construct targeting the 3'UTR of the IE gene. Viral DNA levels in the brains of infected mice were always lower in transgenic mice, even in animals that did not survive. Finally, this work reports an effective strategy to generate transgenic animals producing shRNA from non-retroviral expression vectors. Moreover, these mice are the first transgenic animal models producing shRNA with a significant antiviral effect but without any apparent shRNA toxicity.