Hamada Mohamed Ibrahim

An efficient, microwave/ultrasound-irradiated synthesis of novel chromenopyrimidines has been established. 2-Amino-5-oxo-4-(thiophen-2-yl)-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (1) underwent cyclization reactions with various assorted reagents under sustainable conditions to afford a family of fused pyrimidine derivatives. The proposed structures of the designed fused pyrimidines were confirmed by several spectral techniques. Moreover, the targeted pyrimidines were estimated for their in vitro cytotoxic activities toward three carcinoma cell lines: breast (MCF7), hepatocyte (HepG2), and lung (A549) cancer cell lines, as well as one noncancerous cell line (MCF-10A). Structure-activity relationship (SAR) analyses revealed that derivatives 3 and 7 exhibited the highest potency in inhibiting the growth of cancer cells tested in vitro. Particularly, 3-amino-4-imino-5-(thiophen-2-yl)-3,4,5,7,8,9-hexahydro-6H-chromeno[2,3-d]pyrimidin-6-one (3) displayed a robust impact with IC₅₀ values ranging from 2.02 to 1.61 μM. Interestingly, compound 3 was observed to have low cytotoxicity toward noncancerous cell (MCF-10A) compared to the standard drug (Doxorubicin). Further, quantum chemical computations of the designed molecules utilizing density functional theory (DFT) were conducted and shown to be compatible with the observed antiproliferative properties. Thorough docking investigations revealed that the assembled compounds possess exceptionally low binding energies toward our three selected proteins: 4b3z-Lung, HepG2-2JW2, and 6ENV-MCV-7. Based on these intriguing results, compound 3 could be further evaluated for preclinical screening, potentially paving the way for its utilization as a promising cancer treatment.

An appropriate and efficient Q-tube-assisted ammonium acetate-mediated protocol for the assembly of the hitherto unreported 5-arylazopyrazolo[3,4-b]pyridines was demonstrated. This methodology comprises the cyclocondensation reaction of 5-amino-2-phenyl-4H-pyrazol-3-one with an assortment of arylhydrazonals in an NH₄OAc/AcOH buffer solution operating a Q-tube reactor. This versatile protocol exhibited several outstanding merits: easy work-up, mild conditions, scalability, broad substrate scope, safety (the Q-tube kit is simply for pressing and sealing), and a high atom economy. Consequently, performing such reactions under elevated pressures and utilizing the Q-tube reactor seemed preferable for achieving the required products in comparison to the conventional conditions. Diverse spectroscopic methods and X-ray single-crystal techniques were applied to confirm the proposed structure of the targeted compounds.

Herein, a distinctive dihydroxy ionic liquid ([Py-2OH]OAc) was straightforwardly assembled from the sonication of pyridine with 2-chloropropane-1,3-diol by employing sodium acetate as an ion exchanger. The efficiency of the ([Py-2OH]OAc as a promoter for the sono-synthesis of a novel library of condensed products through DABCO-catalyzed Knoevenagel condensation process of adequate active cyclic methylenes and ninhydrin was next investigated using ultimate greener conditions. All of the reactions studied went cleanly and smoothly, and the resulting Knoevenagel condensation compounds were recovered in high yields without detecting the aldol intermediates in the end products. Compared to traditional strategies, the suggested approach has numerous advantages including mild reaction conditions with no by-products, eco-friendly solvent, outstanding performance in many green metrics, and usability in gram-scale synthesis. The reusability of the ionic liquid was also studied, with an overall retrieved yield of around 97% for seven consecutive runs without any substantial reduction in the performance. The novel obtained compounds were further assessed for their in vitro antitumor potential toward three human tumor cell lines: Colo-205 (colon cancer), MCF-7 (breast cancer), and A549 (lung cancer) by employing the MTT assay, and the findings were evaluated with the reference Doxorubicin. The results demonstrated that the majority of the developed products had potent activities at very low doses. Compounds comprising rhodanine (5) or chromane (12) moieties exhibited the most promising cytotoxic effects toward three cell lines, particularly rhodanine carboxylic acid derivative (5c), showing superior cytotoxic effects against the investigated cell lines compared to the reference drug. Furthermore, automated docking simulation studies were also performed to support the results obtained.

A novel, expedient and effective methodology for the synthesis of distinctly substituted 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline systems has been developed with a new synthetic platform. This process includes ammonium acetate-mediated cyclocondensation reactions of 3-oxo-2-arylhydrazonopropanals with benzosuberone and tetralone precursors, respectively, using the high-pressure Q-tube reactor, which has been found to be superior to both conventional heating and microwave irradiation. The novel protocol benefits from its high atom efficiency, economy, ease of workup, broad substrate scope and is also applicable to gram-scale synthesis. To identify and confirm the newly synthesized targeted compounds, the X-ray single-crystal as well as all possible spectroscopic methods were utilized. The cytotoxicity of the newly synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a–j and 5,6-dihydrobenzo-[h]quinolines derivatives 6a–e were preliminary examined toward three cell lines of human cancer; lung cancer (A549), breast cancer (MCF-7) and colon cancer (HCT-116), by applying the MTT colorimetric assay. The achieved results reflected the promising profile of the prepared compounds in this study against cancer cells and have shown that members from the synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a–j exhibited promising cytotoxicity’s against MCF-7, and A549 cancer cells respectively, while the HCT-116 (colon) cancer cells were inhibited by certain examples of 5,6-dihydrobenzo[h]quinoline derivatives 6c,d. These promising results could serve as a good primary base for further research into the design of anticancer drugs.

An appropriate and efficient Q-tube-assisted palladium-catalyzed strategy for the synthesis of novel, unparalleled diaza-dibenzo[a,e]azulene and diaza-benzo[a]fluorene derivatives has been sophisticated, which includes oxygen and AcOH-induced oxidative C(sp³)–C(sp²) cross-dehydrogenative coupling reactions of 1-amino-2-imino-4-arylpyridine-3-carbonitriles with benzocyclic ketones such as benzosuberone, tetralone, thiochromone, and chromone, respectively. This Q-tube gas purging kit assisted-protocol features safe due to easy pressing and sealing, a wide substrate scope, easy workup and purifying phases, and the use of O₂ as a benign oxidant, in addition to being scalable and having a high atom economy. The suggested mechanistic pathway includes a formal dehydrative step followed by palladium AcOH-induced CH(sp³)–CH(sp²) oxidative cross-coupling. In this study, X-ray crystallographic analysis has been used to authenticate the targeted products.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A facile and effective assembly of several substituted functionalized mono- and bis-[1,2,4]triazolo[1,5-a]pyridines from conveniently attainable 1-amino-2-imino-pyridines has been established. Using microwave irradiation speeds up the reaction efficiently, proceeding with a higher rate and yields than with conventional heating. In the presented protocol, a broad variety of carboxylic acids could be employed effectively to synthesize the respective derivatives via direct metal-free C–N bond construction. Interestingly, other substrates such as aldehydes (or their arylidene malononitriles), phenyl isothiocyanate, glyoxalic acid, and acrylonitriles could also provide the corresponding 1,2,4-triazolo[1,5-a]pyridines successfully. This versatile and convergent approach performs well with both deactivating and activating substrates in an environmentally benign manner compared with other already reported protocols. Other notable merits of the current strategy involve no need for column chromatography, no tedious work-up, and a direct pathway for the fast design of triazolopyridine frameworks. The identity of the newly synthesized compounds was established using several spectroscopic techniques, and X-ray single-crystal tools were employed to authenticate the suggested structures of some representative samples.

A novel and efficient protocol for the synthesis of thiazolo[4,5-c]pyridazine derivatives was developed. The approach utilizes a high pressure Q-Tube reactor to promote cyclocondensation reactions between 3-oxo-2-arylhydrazonopropanals and 4-thiazolidinones. The process has a significantly high atom economy and a broad substrate scope, as well as being applicable to gram scale syntheses. The in vitro cytotoxic activities of the synthesized thiazolo[4,5-c]pyridazine derivatives were examined utilizing a MTT colorimetric assay with doxorubicin as a reference anti-cancer drug and three human cancer cell lines including HCT-116 (colon), MCF-7 (breast) and A549 (lung). The results show that thiazolopyridazines 7c, h, k and p have high cytotoxic activity against the MCF-7 cell line with respective IC₅₀ values of 14.34, 10.39, 15.43 and 13.60 μM. Moreover, the thiazolopyridazine derivative 7s also show promising cytotoxic activity against the HCT-116 cell line with IC₅₀ = 6.90 μM . Observations made in this effort serve as a basis for further investigations into the design and preparation of new anti-cancer drugs.