Design and Synthesis of New bis-oxindole and Spiro(triazole-oxindole) as CDK4 Inhibitors with Potent Anti-breast Cancer Activity.

BACKGROUND: Since CDKs have been demonstrated to be overexpressed in a wide spectrum of human malignancies, their inhibition has been cited as an effective technique for anticancer drug development. METHODS: In this context, new bis-oxindole/spiro-triazole-oxindole anti-breast cancer drugs with potential CDK4 inhibitory effects were produced in this work. The novel series of bis-oxindole/spirotriazole- oxindole were synthesized from the reaction of bis-oxindole with the aniline derivatives then followed by 1,3-dipolar cycloaddition of hydrazonoyl chloride. RESULTS: The structure of these bis-oxindole/spiro-triazole-oxindole series was proven based on their spectral analyses. Most bis-oxindole and bis-spiro-triazole-oxindole compounds effectively inhibited the growth of MCF-7 (IC50 = 2.81-17.61 µM) and MDA-MB-231 (IC50 = 3.23-7.98 µM) breast cancer cell lines with low inhibitory activity against normal WI-38 cells. While the reference doxorubicin showed IC50 values of 7.43 µM against MCF-7 and 5.71 µM against the MDA-MB-231 cell line. Additionally, compounds 3b, 3c, 6b, and 6d revealed significant anti-CDK4 activity (IC50 = 0.157- 0.618 µM) compared to palbociclib (IC50 = 0.071 µM). Subsequent mechanistic investigations demonstrated that 3c was able to trigger tumor cell death through the induction of apoptosis. Moreover, it stimulated cancer cell cycle arrest in the G1 phase. Furthermore, western blotting disclosed that the 3c-induced cell cycle arrest may be mediated through p21 upregulation. CONCLUSION: According to all of the findings, bis-oxindole 3c shows promise as a cancer treatment targeting CDK4.

Preparation of carboxymethyl cellulose/polyvinyl alcohol wound dressing composite immobilized with anthocyanin extract for colorimetric monitoring of wound healing and prevention of wound infection.

Novel aerogel-like wound dressing able to sense the healing progress was developed. Anthocyanins (Ac) have been reported as a significant pH-sensory extract with various biological activities. Herein, anthocyanins were extracted from red-cabbage (Brassica oleracea L. Var. capitata). The anthocyanin probe was integrated as a water-soluble direct dye at various concentrations into carboxymethyl cellulose/polyvinyl alcohol composite in the presence of potassium aluminum sulfate mordant. The generated composites were then freeze-dried to provide the corresponding aerogel-like smart wound dressing to function as an antibacterial and biochromic bulk presenting a comfort dressing biosensor to monitor the progress of a wound healing. Reducing the pH value of a wound mimicking fluid resulted in a hypsochromic shift from 592 to 446 nm. The halochromic activity of anthocyanin showed colorimetric changes from purple to pink. The colorimetric measurements of the prepared anthocyanin-containing aerogel-like diagnostic assay were explored by CIE Lab coordinates and UV-Vis absorption spectra. The effects of the anthocyanin content on the morphology, stiffness, air-permeability, and mechanical behavior of the aerogel-like wound dress were explored by various analytical methods. Both cytotoxicity and antibacterial activity of were investigated.

Preparation of photoluminescent nanocomposite ink for detection and mapping of fingermarks.

Simple and efficient detection and mapping method based on a strong turn-on fluorescent pigment was developed for fingerprint analysis. We present a phosphor powder characterized by strong emission which is useful to achieve better fingerprint detection on multicolored or photoluminescent surfaces, such as currency notes characterized by optically changeable inks and highly fluorescent positions, because it offers better contrast and reduce the difficulty of background interference. Novel photochromic ink was prepared to establish a fingerprinted colorless film onto cellulose documents with green emission for anticounterfeiting applications as illustrated by photoluminescence spectra. Inorganic/organic nanoscale composite ink was prepared from rare-earth doped aluminate phosphor nanoparticles (PNPs; 27-49 nm) dispersed in a polyacrylic acid binding agent. PNPs were dispersed efficiently in polyacrylic acid to generate a colorless mark. The produced photochromic inks were spray-coated onto off-white paper sheets enclosing invisible fingermarks, and then exposed to thermofixation. Photochromic film was detected on paper surface presenting a transparent appearance under visible daylight and switchable to green under UV light. The CIE Lab parameters and photoluminescence spectra were studied under visible light and ultraviolet irradiation. The fingerprinted sheets showed fluorescence band at 517 nm upon excitation at 366 nm, showing a bathochromic shift and reversible photochromism without fatigue. The morphologies of pigment phosphor particles and fingerprinted sheets were inspected. The rheological properties of ink and mechanical behavior of the fingerprinted paper samples were explored. HIGHLIGHTS: Novel smart ink with alkaline-earth aluminate and polyacrylic acid was developed. Dual-mode fluorescent photochromism was presented for latent fingerprint analysis. Off-white fingerprinted films under daylight showed color change to green under UV. Fluorescence band monitored at 517 nm upon excitation at 366 nm. Fluorescent fingermark on paper sheets demonstrated good photostability.

Synthesis of (tricyanofuran-3-ylmethylene)hydrazinyl thiazole-containing chromophore: A study of its photophysical properties, solvatochromism, and TD-DFT computations.

The chromophore 2-2-(3-cyano-5,5-dimethyl-4-((2-[thiazol-2-yl]hydrazono)methyl)-furan-2(5H)-ylidene)malononitrile (TzHTCF) was prepared by diazo-coupling of diazotized 2-aminothiazole with 3-cyano-2-(dicyanomethylene)-4,5,5-trimethylfuran (TCF). The TzHTCF absorption solvatochromism, in different polarity solvents, demonstrated a ΔEmax = +4.74 in which the positive sign implied the occurrence of a red shift and the TzHTCF lowest excited state was more polar than its ground state. In addition, the TzHTCF fluorescence spectrum produced a λem in the 416-670 nm range and was more dependent on the solvent polarity than the absorption λmax , despite both exhibiting a red shift of 24 and 254 nm, respectively. To discover the Stokes shift ( ∆ ν ¯ ) behaviour of the TzHTCF derivative, Lippert-Mataga and linear solvation-energy relationship (LSER) formulations were utilized in which the LSER approach displayed better results than the Lippert-Mataga method (R2 = 0.9931). Furthermore, the LSER showed that the absorption and fluorescence solvatochromic behaviours were dependent on the solvent's hydrogen-bond donor (α) and acceptor (ß), along with the solvent's polarizability (π*). Moreover, DFT calculations showed that TzHTCF has a planar configuration and its simulated absorption and emission spectra in dimethyl sulphoxide revealed that λmax primarily originated from the HOMO→LUMO and HOMO-1→LUMO transitions, respectively.