New (S)-verbenone-isoxazoline-1,3,4-thiadiazole hybrids: synthesis, anticancer activity and apoptosis-inducing effect.

Background: This study aimed to develop novel isoxazoline-1,3,4-thiadiazole hybrids from (S)-verbenone for potential anticancer treatment, particularly focusing on cytotoxic and apoptotic effects in hormone-sensitive MCF-7 and triple-negative MDA-MB-231 breast cancer cells. Methods & results: (S)-verbenone was used to synthesize hybrids through 1,3-dipolar cycloaddition, followed by thorough characterization. The compounds were screened across cancer cell lines, showing significant anticancer effects. Compound 8b notably induced apoptosis via the caspase-3/7 pathway and cell cycle arrest, displaying noteworthy cytotoxicity against MCF-7 and MDA-MB-231 cells. Conclusion: These findings underscore the potential of (S)-verbenone isoxazoline-1,3,4-thiadiazole derivatives for breast cancer therapy due to their remarkable apoptotic activity. This study highlights a promising avenue for advancing breast cancer treatment using these derivatives, founded on (S)-verbenone, showcasing their distinct potential for inducing apoptosis.

Crystallographic study, biological assessment and POM/Docking studies of pyrazoles-sulfonamide hybrids (PSH): Identification of a combined Antibacterial/Antiviral pharmacophore sites leading to in-silico screening the anti-Covid-19 activity.

The discovery and development of new potent antimicrobial and antioxidant agents is an essential lever to protect living beings against pathogenic microorganisms and free radicals. In this regard, new functionalized pyrazoles have been synthesized using a simple and accessible approach. The synthesized aminobenzoylpyrazoles 3a-h and pyrazole-sulfonamides 4a-g were obtained in good yields and were evaluated in vitro for their antimicrobial and antioxidant activities. The structures of the synthesized compounds were determined using IR, NMR, and mass spectrometry. The structure of the compound 4b was further confirmed by single crystal X-ray diffraction. The results of the in vitro screening show that the synthesized pyrazoles 3 and 4 exhibit a promising antimicrobial and antioxidant activities. Among the tested compounds, pyrazoles 3a, 3f, 4e, 4f, and 4g have exhibited remarkable antimicrobial activity against some microorganisms. In addition, compounds 3a, 3c, 3e, 4a, 4d, 4f, and 4g have shown a significant antioxidant activity in comparison with the standard butylhydroxytoluene (BHT). Hence, compounds 3a, 4f, and 4g represent interesting dual acting antimicrobial and antioxidant agents. In fact, pyrazole derivatives bearing sulfonamide moiety (4a-g) have displayed an important antimicrobial activity compared to pyrazoles 3a-h, this finding could be attributed to the synergistic effect of the pyrazole and sulfonamide pharmacophores. Furthermore, Molecular docking results revealed a good interaction of the synthesized compounds with the target proteins and provided important information about their interaction modes with the target enzyme. The results of the POM bioinformatics investigations (Petra, Osiris, Molinspiration) show that the studied heterocycles present a very good non toxicity profile, an excellent bioavailability, and pharmacokinetics. Finally, an antiviral pharmacophore (O δ-, O δ-) was evaluated in the POM investigations and deserves all our attention to be tested against Covid-19 and its Omicron and Delta mutants.

1-(3-p-Tolyl-isoxazol-5-yl)cyclo-hexa-nol.

The title compound, C(16)H(19)NO(2), contains two mol-ecules in the asymmetric unit. Each mol-ecule is composed of three inter-connected rings, two essentially planar rings, viz. the isoxazole and the methyl-benzyl aromatic ring [maximum deviations of 0.0027 (13) and 0.0031 (19) Šfrom the isoxazole and methylbenzyl ring planes, respectively, in the first molecule, 0.0018 (12) and 0.019 (2) Šin the second molecule], and one cyclo-hexa-nol ring having a chair conformation. Although the two mol-ecules have similar bond distances and angles, they differ in the orientation of the cyclo-hexa-nol ring with respect to the tolyl-isoxazole unit. In the first mol-ecule, the dihedral angle between the isoxazole and methyl-benzyl rings is 22.03 (8)° and between the isoxazole and cyclo-hexa-nol rings is 30.15 (8)°. The corresponding values in the second mol-ecule are 6.13 (10) and 88.44 (8)°, respectively. In the crystal, the molecules are linked by O-H⋯O and O-H⋯N hydrogen bonds, building up a zigzag chain parallel to the a axis.