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The specific aims of this study is to synthesize and to study the possible mechanism of N'-benzoylsalicylhydrazide derivatives as an antituberculosis agent through InhA (Enoyl acyl carrier protein reductase) inhibition using in silico method. Five analogues of N'-benzoylsalicylhydrazide were synthesized using microwave irradiation from methyl salicylate as starting material, which yielded 80-90% product on average. This indicates a considerable improvement in terms of effectivity and efficiency, compared to the more conventional method using reflux condition. Characterization of the compounds were subsequently carried out by UV, FTIR, 1 H-NMR, 13 C-NMR spectroscopy, which confirmed that the compounds had been successfully synthesized. Ultimately, molecular docking was performed using Molegro Virtual Docker (MVD) on the active site of InhA enzyme to predict the activity of the compounds. The results showed that all compounds performed comparatively well against N-(4-Methylbenzoyl)-4benzylpiperidine as the native ligand and also yielded lower docking score than isoniazide (INH). From this study it can be concluded that N'-benzoylsalicylhydrazide derivatives could be synthesized using microwave irradiation with good product yield and all of the synthesized analogues are suggested to possess antituberculosis activity via InhA enzyme inhibition. In vitro activity will have to be determined in the future to validate whether N'-benzoylsalicylhydrazide derivatives perform well as a potential antituberculosis agent.

In silico study was performed to predict the possibility of 1-benzyl-3-benzoylurea and 22 analogs as anticancer drug candidates, via VEGFR2 inhibition. Molecular docking studies against VEGFR2 receptor revealed that all of designed compounds have better score than the lead compound, of which three analogs (p-nitro, p-methoxy, and p-ethyl) were considered optimal among other compounds (< -90 kcal mol−1). However, this result was not comparable to lenvatinib, which acts as native ligand of the receptor (-118.62 kcal mol−1). Docking poses analysis showed that 1-benzyl-3-benzoylurea analogs failed to completely occupy VEGFR2 binding site. Therefore, it is argued that this has caused the non-optimal docking score of designed compounds. Furthermore, these compounds passed five different drug-likeness criteria successfully and were predicted to be orally bioavailable in rat. Ultimately, most of the analogs were predicted to have good ADMET characteristics, notably in terms of GI absorption and the absence of P-gp interaction, and low toxicity in rat. This study can be used as a starting point to validate this model by synthesis, in vitro and in vivo assay to validate the activity of 1-benzyl-3-benzoylurea and its analogs as potential anticancer candidate.

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Objectives This study aims to synthesize a series of benzoxazines (1–5) to be examined as an epidermal growth factor receptor (EGFR) inhibitor by in-silico study. The overexpression of EGFR causes the growth of normal lung cells to become uncontrollable, which may lead to cancer formation. We also conducted the absorption, distribution, metabolism, excretions and toxicity (ADMET) properties evaluation and also examined in vitro anticancer assay on human lung cancer cells line, which is A549. Methods Benzoxazines (1–5) were synthesized by reacting anthranilic acid and benzoyl chlorides. The structures of the compounds were determined with 1H, 13C-NMR, HRMS, UV and FT-IR spectrometric methods. Prediction of ADMET was using online pkCSM, and the molecular docking studies were using MVD with EGFR-TKIs as the target (PDB ID: 1M17). In vitro assay of anticancer activity was performed by MTT assay. Results Compounds 1–5 were successfully synthesized in good yields (71–84%). The ADMET prediction showed that benzoxazines are able to be absorbed through GIT, metabolized by CYP 450, and not hepatotoxic. The title compounds have a greater Moldock Score than Erlotinib, and 3 has the highest activity against A549 compared with other benzoxazines, IC50=36.6 μg/mL. Conclusions Compound (3) more active as anticancer against Human cancer cells line compared with other benzoxazines.