1,2,3-Triazole-containing hybrids as potential anticancer agents: Current developments, action mechanisms and structure-activity relationships.

Laboratory control of antimicrobial therapy

Pharmaceutical prospects of naturally occurring quinazolinone and its derivatives

Oxidative stress is one of the main causes of significant severe diseases. The discovery of new potent antioxidants with high efficiency and low toxicity is a great demand in the field of medicinal...

Design, synthesis, molecular modelling and biological evaluation of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors.

Recent advancements in the development of bioactive pyrazoline derivatives.

Carbodiimide that was generated from the condensation reaction of iminophosphorane with phenylisocyanate was allowed to react with different phosphorus nucleophiles. Thus, the in situ resulted heterocumulene reacted with dialkylhydrogenphosphonates in tetrahydrofuran (THF)/FeCl(3) /H(2) O system to give fused pyrrole- (≈14%) and pyrimidinephosphonates (≈57%). On the other hand, with tris-(dialkyl)aminophosphines, the reaction afforded the corresponding hexaalkylphosphinic diamides as a water-sensitive fine powder, quite stable for a few days in a desiccator. When a protonating agent was present in the reaction medium, the reaction was markedly accelerated leading to the formation of the phosphamides. Next, some saturated and unsaturated Horner-Emmons reagents were applied in situ to the same carbodiimide to obtain more phosphorylated N-heterocycles. The analgesic and antiinflammatory activities of the newly synthesized compounds were investigated and showed significant activities. Finally, we further estimated the antitumor activity of five new phosphonates against four carcinoma cell lines.

Carbodiimides in the synthesis of enamino- and α-aminophosphonates as peptidomimetics of analgesic/antiinflammatory and anticancer agents.

Investigations in the discovery of tyrosinase enzyme inhibitors have the potential to design novel anti-cancer drugs. A variety of novel bivalent pyrazolinyl triazoles 5–7 were synthesized and identified. The bis-acetyl triazole 3 was accomplished via two-step process first by preparation of diazide 2 followed its coupling reaction with acetylacetone in basic medium. The Claisen–Schmidt condensation reaction of 3 with two moles equivalent of benzaldehyde produces the corresponding bis-α, β-unsaturated ketone 4. Treatment of Schiff base 4 with excess hydrazine hydrate in either acetic acid or ethanol/DMF afforded the bis-N-acetylpyrazline 5 or bis-pyrazoline 6, respectively. Finally, treatment of 6 with two derivatives of isothiocyanate analog gives the bis-N-thioamide pyrazolines 7a and 7b. The synthesized compounds were evaluated as anti-tumor candidates against three human cancer cell lines (MCF-7, HepG2, and HCT-116). The bioscreening evaluation showed that compounds 7a and 6 had a significant antineoplastic potencies (IC50: 32.26 and 57.06 µg/mL) against breast MCF-7 and hepatic HepG2 cancerous cell lines, respectively, in relative to the standard drug, 5-fluorouracil. Molecular docking studies of the synthesized compounds were investigated as VEGFR2 TK inhibitors.

Synthesis, molecular docking, and evaluation of novel bivalent pyrazolinyl-1,2,3-triazoles as potential VEGFR TK inhibitors and anti-cancer agents

Based on the prediction results (PASS program), a new series of α-aminophosphonate derivatives and azaphosphones was synthesized and evaluated as antitumor agents against breast-, cervical-, liver, and colon cancer diseases. The analgesic/antiinflammatory properties of the new phosphorylated pyrazoles were also investigated. The study demonstrated an efficient site selective method for making condensation products of phosphonate derivatives in high yields from carbodiimides and different types of HE reagents (74–78%) as well as dialkyl phosphites (54–65%) and hexaalkyltriamidophosphites (80–85%). Their antitumor properties against four carcinoma cell lines representing human-liver (HEPG2), -colon (HCT116), -breast (MCF7), and -cervix (HeLa) were investigated. The results showed that at least two out of the five tested phosphonates exhibited remarkable antitumor activity (IC50: 4.15–6.95 μM mL−1) when compared to the standard drugs (IC50: 5.7–9.3 μM mL−1). Nevertheless, four phosphonate products showed an analgesic capacity >80%, when compared to aspirin (73%) at the same dose of 100 mg kg−1. Furthermore, QSAR results indicated that the fused azaphosphones, thiazolopyrimidine- and pyridine-α-aminophosphonate derivatives (6 of 11 tested compounds), possess inflammatory inhibitory potency (99–117%) when compared to the standard drug (100%) after 360 min.

Carbodiimides – key mediators in the synthesis of novel cytotoxic and analgesic/antiinflammatory motifs based on α-amino-, enaminophosphonates, and azaphosphones

3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2.

Currently, limited therapeutic options are available for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). We have developed a set of pyrazine-based small molecules. A series of pyrazine conjugates was synthesized by microwave-assisted click chemistry and benzotriazole chemistry. All the synthesized conjugates were screened against the SAR-CoV-2 virus and their cytotoxicity was determined. Computational studies were carried out to validate the biological data. Some of the pyrazine-triazole conjugates (5 d-g) and (S)-N-(1-(benzo[d]thiazol-2-yl)-2-phenylethyl)pyrazine-2-carboxamide 12 i show significant potency against SARS-CoV-2 among the synthesized conjugates. The selectivity index (SI) of potent conjugates indicates significant efficacy compared to the reference drug (Favipiravir).

Mohamed S. Bekheit

Papers

Carbodiimides in the synthesis of enamino- and α-aminophosphonates as peptidomimetics of analgesic/antiinflammatory and anticancer agents.

Synthesis, molecular docking, and evaluation of novel bivalent pyrazolinyl-1,2,3-triazoles as potential VEGFR TK inhibitors and anti-cancer agents

Carbodiimides – key mediators in the synthesis of novel cytotoxic and analgesic/antiinflammatory motifs based on α-amino-, enaminophosphonates, and azaphosphones

3-Alkenyl-2-oxindoles: Synthesis, antiproliferative and antiviral properties against SARS-CoV-2.

New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS-CoV-2.