Letters in Organic Chemistry - Volume 18, Issue 1, 2021

In this work, 1,2,4-triazine derivatives were synthesized and evaluated for anticancer activities. Series of 1,2,4-triazine derivatives (4a, b) were prepared via the reaction of N-benzoyl glycine (1) with aromatic aldehydes in the presence of fused sodium acetate and acetic anhydride to give 1,3- oxazolinone derivatives (2a, b), followed by condensation with 1-(ethoxycarbonyl) hydrazine (3) in glacial acetic acid. Compounds (4a, b) then reacted with acetic anhydride, ethyl chloroacetate and 2,4- dinitrophenyl hydrazine yielded the corresponding N-acetyl derivatives (5a, b), N-(ethoxycarbonyl) methyl derivative (6) and 1,2-disubstituted hydrazine (7), respectively. The structures of the 1,2,4- triazine derivatives were confirmed by IR, ¹H, ¹³C NMR, MS, and elemental analyses. Anticancer activity of some 1,2,4-triazine derivatives (4-7) has been investigated. The results revealed that compounds 4a (IC50= 2.7μM), 5a (IC50= 1.5μM), and 5b (IC50= 3.9μM) show promising inhibitory growth efficacy compared to a standard antitumor drug (IC50= 4.6μM). These three compounds can be considered as potential agents against human hepatocellular carcinoma cell lines (HepG-2).

The synthesis of a third generation dronic acid, zoledronic acid by the reaction of imidazol- 1-yl-acetic acid with phosphorus trichloride/phosphorous acid in diethyl carbonate (DEC) as a “green” solvent, and in DEC – methanesulfonic acid (MSA) solvent mixtures is described. The earlier not “green” and expensive MSA and sulfolane solvents may be replaced by DEC.

A three-component synthesis of novel 5-phenyl-2-(thiophen-2-yl)-4-(trifluoromethyl)-5Hindeno [1,2-b] [1,8] naphthyridin-6(11H)-one derivatives (4a-n) was prepared using 6-phenyl/ (thiophen- 2-yl)-4-(trifluoromethyl)pyridin-2-amine, 1H-indene-1,3(2H)-dione, and aryl aldehyde using 40% aq. HF with good yield. All the synthesized compounds were screened against Gram-positive and Gram-negative bacterial strains and different Candida strains by the well diffusion method. Compounds 4c, 4f, and 4g showed promising activity on Bacillus subtilis strain and compounds 4c and 4g showed promising activity towards Candida albicans strains.

In this study, the antioxidant property of eight new azomethine derivatives underwent theoretical and experimental investigations. Azomethines have antioxidant activity. This is the first time the molecular structures and antioxidant property of these derivatives have been studied. The molecular structures were optimized using Density functional theory (DFT). The Bond Dissociation Enthalpy (BDE), Mulliken Charges, NBO analysis, Ionization Potential (IP), Electron Affinities (EA), HOMO and LUMO energies, Hardness (η), Softness (S), Electronegativity (μ), Electrophilic Index (ω), Electron Donating Power (ω^-), Electron Accepting Power (ω⁺), and Energy Gap (Eg) were calculated in order to deduce scavenging action of the eight new synthesized azomethines (DIA-3,4,5,6,7,8,9,10). Spin density calculations and NBO analysis were also carried out to understand the antioxidant activity mechanism. These molecules have high antioxidant potential due to the planarity and formation of intramolecular hydrogen bonds. Experimental investigations establish high antioxidant and antitumor activities of the synthesized azomethine derivatives.

A selected set of new N1-(indan-5-yl)amidrazones 4a-p, encompassing piperazines or related amines, has been prepared via interaction of the hydrazonoyl chloride 3 (derived from 5-aminoindane) with the appropriate sec-cyclic amine in the presence of triethylamine. Their suggested structures are supported by IR, ¹H NMR, ¹³C NMR, high-resolution MS (ESI) spectral data, and further confirmed by single-crystal X-ray crystallography for 4k. These novel compounds were screened for their antitumor activity against breast cancer cells (MCF7 and T47D); amongst all of them, only compound 4o, incorporating N-(pyrimidin-2-yl)piperazine, was fairly active with IC50 values of 69 μM and 61 μM, respectively.

A new class of phenylbenzo[4,5]thiazolo[3,2-a]pyrano[2,3-d]pyrimidin-5-one and pyrano[ 2,3-d]thiazolo[3,2-a]pyrimidine-5-one derivatives have been synthesized via one-pot threecomponent reaction of 2-hydroxy-4H-benzo[4,5]thiazolo[3,2-a]pyrimidin-4-one and 7-hydroxy-5Hthiazolo[ 3,2-a]pyrimidin-5-one with various aromatic aldehydes and (E)-N-methyl-1-(methylthio)-2- nitroethenamine under microwave irradiation. This transformation involves the formation of thiazole or benzothiazole fused pyranopyrimidinone ring by the formation of two C-C bonds and one C-O bond in a single synthetic operation. This rapid one-pot reaction does not require a catalyst, it is solvent-free, avoids chromatographic purification, and provides good yields. The synthesized compounds were evaluated for their antiproliferative activity against four cancer cell lines, namely DU 145 (prostate cancer), MDA-MB-231 (breast cancer), Hela (Human cervical cancer), HT-29 (Human colon cancer) and HEK293 (human embryonic kidney cells). The results demonstrated that synthesized compounds were selective in its cytotoxicity to cancer cells compared to normal HEK293 cells. Compound 12h exhibited the most potent antiproliferative activity against the tested cell lines, while other test compounds showed weak or moderate antiproliferative activity, among them 12d, 12e and 14d displayed showed IC50 values in the low micromolar range. Molecular docking studies revealed that these active heterocyclic molecules bind selectively in the colchicine binding site of tubulin polymer.

In this paper, the synthesis of the A-B bicyclic ring structure 3 of the natural product Stemocurtisine is described. The synthesis was accomplished in seven synthetic steps from commercially available L-glutamic acid. The key step involved a borono-Mannich reaction between the hemiaminal 6 and trans-β-styryl boronic acid and trans-β-styrylpotassiumtrifluoroborate to prepare the cis diene 4. Attempts to prepare the A-B-C ring compound 2 via intramolecular epoxide ring opening followed by rearrangement under different basic conditions were unsuccessful. The only unreactive starting material was recovered.

In this report, SO3H-functionalized Carbon nanoparticles (Pine-SO3H) with high acid density have been synthesized by the thermal treatment of sulfuric acid with Pine-Cone as carbon-based at 180°C in a sealed autoclave in a one-step procedure. The resulted Nanocatalyst was characterized by FT-IR, TGA, XRD, FE-SEM and elemental analysis (EA). The result of characterization was shown that the carbon-based acid is amorphous with polycyclic aromatic carbon sheets attached plentiful -OH, -COOH, and -SO3H groups. The catalytic activities of Pine-SO3H was investigated in the highly efficient synthesis of pyrano[2,3-c] pyrazole, amino-benzochromenes, amidoalkyl naphthol and 5-arylidene-2,4-thiazolidinedione derivatives. The application of Pine-SO3H in the synthesis offers several advantages such as simple procedure with an easy work-up, recoverable catalyst, mild condition, eco-friendliness, excellent yields, short reaction times and use of an inexpensive catalyst.