This study provides the first account of the molecular impact of UM-164 binding on lyn protein using various computational approaches.

Proteases are validated drug target for inhibition of Plasmodium falciparum, the most virulent malaria parasite. This study guided by previous reports, designed trimethoxy benzaldehyde chalcone derivatives as potential protease inhibitors and antimalarial agents. They were synthesized by Schmidt-Claisen condensation reaction. The structures of these compounds were established using Fourier transform infrared (FT-IR), Proton, Carbon-13, as well as twodimensional nuclear magnetic resonance (NMR) spectroscopy, and Mass Spectrometry (MS). The synthesized compounds were screened for in-vivo antimalarial activity in mice infected with Plasmodium berghei parasite, using curative model. (E)-1-(2,4-dimethoxyphenyl)-3-(2,3,4trimethoxy-phenyl) prop-2-en-1-one (P2) displayed a significant activity, with activity comparable to that of quinine (10 mgkg-1) and chloroquine (25 mg kg-1) at a dose of 100 mgkg-1 in the curative test. However, (E)-1,3-bis(2,3,4-trimethoxyphenyl) prop-2-en-1-one (P1) and (E)-1-(2,4-dichlorophenyl)-3-(2,3,4-trimethoxyphenyl) prop-2-en-1-one (P13) did not show any significant activity (p < 0.05). Compound P2 was found to be devoid of electron deficient ring A (benzaldehyde ring). This suggests that, electron density on the rings are not determinants for antimalarial activity of the chalcone as proposed earlier and, present compound P2 as a candidate for further optimization and evaluation for prophylactic and suppressive activities.

We conducted a comparative study on the development of two synthetic methods. The solvent-free synthesis is a green chemistry method developed in a bid to ameliorate environmental adverse effects of the conventional solvent-based synthesis. The synthesis of novel dichloro and polymethoxy p-nitrophenylhydrazones through solvent free technique gave moderate to high yields which were however lower than those of the solvent-based method. The established solvent-free approach has several benefits, including universality and simplicity of the approach, catalyst-free conditions, non-use of an organic solvent, quick reaction time, fast and efficient workup, and un-solvated pure products in moderate to high yields.

Objectives: Chalcones have been identified as potential antitumor agents with a novel target, the tubulin. The aim of the study was to synthesize a piperonal substituted chalcone and evaluate its in vivo antitumor activity. Materials and Methods: Piperonal substituted chalcone was synthesized using Claisen-Schmidt condensation and characterized using various spectroscopic techniques. The lethal dose (LD50) of the synthesized compound was estimated using OECD-425 guidelines in rats. Antitumor activity of the synthesized compound was evaluated on 1-methyl nitrosourea (MNU)-induced mammary tumor in female Wistar rats. Histological evaluation was used to confirm tumor induction and assess treatment with the synthesized compound. The possible mechanism of action of the synthesized compound was elucidated in silico using molecular docking. Results: The compound was synthesized and named C2. C2 was found to be relatively safe with LD50 >2000 mg/kg orally. Moreover, C2 exhibited remarkable antitumor activity, at all the tested doses in a dose dependent manner. Histological evaluation of the MNU-induced mammary tumor rats treated with C2 displayed fewer signs of hyperplasia and small numbers of connective tissue with larger lobules when compared with the untreated group. In silico tubulin-binding interactions revealed that the kinetics of C2 binding to tubulin was like that of colchicine. Comparison of crystal structures of tubulin-C2 and tubulin-colchicine complexes showed that the binding mode of C2 to tubulin was like that of colchicine to tubulin and produced the same conformational changes on the tubulin structure as colchicine. Conclusion: The synthesized chalcone demonstrated remarkable antitumor activities in MNU-induced mammary tumors in rats possibly through inhibition of tubulin polymerization.

Ethnobotanical information indicates that Indigofera conferta is used in northern Nigeria for the management of poisonous snakebites and the methanol extract was previously reported to have antivenin activity. In this study, we report the isolation of an oxyprenylated bioactive secondary metabolite; 2',4'-dihydroxy-4-prenyloxychalcone from the chloroform fraction of the aerial parts