Introduction: Pluchea indica is known to have diverse pharmacological properties, including anti-inflammatory, antioxidant, antimicrobial, and anticancer activities. However, there is a pressing need to thoroughly investigate the molecular interactions between P. indica compounds and peroxisome proliferator-activated receptor gamma (PPARG). This study aimed to elucidate the molecular mechanisms behind P. indica and PPARG, and its potential implications for diabetes mellitus. Methods: The computational investigation employed Pharmacological Network pharmacology, homology modeling, deep learning docking, and molecular dynamics to explore the active compounds and targets within P. indica against the PPARG. Results: Three active compounds were identified namely pinoresinol, syringaresinol, and plucheoside A, all of which complied with the Lipinski rule of five. The deep learning-based pose scores were determined as follows: Pinoresinol 0.55, syringaresinol 0.32, and plucheoside A 0.44. Additionally, protein-protein interactions were observed with PPARG and associated with the PPAR signaling pathway. Molecular dynamics simulation analysis showed the stability of the three compounds over a 100 ns period. Free energy calculations using Molecular Mechanics-Generalized Born and Surface Area (MM-GBSA) yielded ΔG values of -44.39 kcal/mol, -51.83 kcal/mol, and -40.27 kcal/mol for pinoresinol, syringaresinol, and plucheoside A, respectively. Conclusion: Pluchea indica might be developed to treat various diseases, particularly those involving the PPARG signaling pathway. It suggests the possibility of being developed as a focused medication for diabetes.

2-Hydroxy-N′-(4-fluorobenzoyl)benzohydrazide was synthesized in two steps using methyl salicylate as the starting material. The reaction took place via microwave-aided hydrazinolysis, followed by acylation using 4-fluorobenzoyl chloride at low temperature to yield the target compound.

Objectives: This study aimed to identify novel antimalarial compounds based on allosteric inhibitor of prolyl-tRNA synthetase using hierarchical virtual screening. Materials and Methods: Pharmacophore model was designed initially, based on the structure-activity relationships data between several pyrazole-urea analogues and their IC50 enzymatic value. The model obtained was applied to screen ZINC15 database, after which followed by drug-likeness, toxicophore, and PAINS filter. The hit compounds were docked against P. falciparum prolyl-tRNA synthetase enzyme, using validated docking method. The resulting docking poses were ranked based on the docking score and re-evaluated based on the pharmacophore criteria. Top five compounds were obtained from this step and then evaluated using molecular dynamics simulation to verify its stability and hydrogen bond dynamics over 50 nanoseconds. MM-PBSA analysis was also performed to estimate their binding free energy. Ultimately, their potential bioactivity as antimalarial candidates have been verified against 3D7 strain. Results: The results showed that all five compounds obtained from virtual screening possess micromolar potency in vitro. Two compounds (ZINC 1029449 and ZINC1029453), yield high antimalarial activity (0.44 and 0.72 μM, respectively) Conclusions: Overall, the virtual screening approach has successfully produced lead compounds which can be further optimized to be antimalarial agents.

Numerous studies have documented the potential of coffee to aid in asthma prevention. Nevertheless, research into how coffee influences asthma management has not been available. One known mechanism by which asthma medications work involves inhibiting 5-lipoxygenase (5-LOX) activity. This study aims to determine the potency of Coffea canephora var. Robusta extract (CRE), Coffea arabica extract (CAE), and caffeine are the primary isolates against 5-LOX activity. Extraction was performed by a reflux procedure using 96% ethanol with a sample-total solvent ratio of 1 : 10, an extraction time of 1 hour, and the extraction was conducted in triplicate. Fractionation was carried out by liquid-liquid partition using a chloroform-water system. Caffeine further purification was performed by the sublimation method, and the inhibition of 5-LOX activity was evaluated using the spectrophotometric method at λ = 234 nm. Apigenin was used as a positive control. From the experiment conducted, the IC50 of the CRE, CAE, caffeine, and apigenin against 5-LOX was 32.2 ± 1.4, 42.1 ± 2.3, 14.3 ± 1.6, and 7.4 ± 1.7 µg/mL, respectively. Continued efforts to isolate bioactive compounds from coffee extract led to the discovery of caffeine, which exhibited a more potent inhibitory effect on 5-LOX. The inhibition of 5-LOX activity by caffeine occurs in a non-competitive manner.

J. Pharm. Pharmacogn. Res., vol. 11, no. 6, pp. 1123-1136, Nov-Dec 2023. DOI: https://doi.org/10.56499/jppres23.1718_11.6.1123 Original Article QSAR study of benzylidene hydrazine benzamides derivatives with in vitro anticancer activity against human lung cancer cell line A459 [Estudio QSAR de derivados de benzilideno hidrazina benzamidas con actividad anticancerígena in vitro frente a la línea celular de cáncer de QSAR study of benzylidene hydrazine benzamides derivatives with in vitro anticancer activity against human lung cancer cell line A459

Malaria adalah salah satu penyakit infeksi yang memiliki tingkat kematian cukup tinggi. Penyakit ini disebabkan oleh parasit Plasmodium yang ditularkan melalui gigitan nyamuk Anopheles betina. Sejak tahun 2004 obat pilihan utama untuk malaria adalah obat kombinasi artemisinin (ACT). Salah satu obat yang dapat dikembangkan sebagai calon obat antimalaria saat ini yaitu halofuginon dan turunannya. Halofuginon bekerja dengan metode inhibisi enzim prolil-tRNA sintetase pada Plasmodium falciparum (PfPRS). Penelitian ini bertujuan untuk mengoptimasi struktur senyawa halofuginon untuk mendapatkan senyawa baru yang poten dan tidak toksik. Tahapan modifikasi senyawa dilakukan dengan bantuan webserver ADMETopt untuk memperoleh beberapa rekomendasi senyawa derivat. Senyawa turunan ini kemudian disikrining menggunakan webserver SwissADME dengan melihat parameter absorbsi serta deteksi gugus fungsi PAINS dan toksikofor. Senyawa yang memenuhi kriteria dilakukan molecular docking untuk mendapatkan nilai binding energy dan untuk mengetahui interaksi ikatannya dengan residu asam amino enzim PRS. Hasil penelitian ini diperoleh 2 senyawa: 8‐[3‐(7‐bromo‐6‐kloro‐4‐okso‐3,4‐dihidrokuinazolin‐3‐il)‐2‐oksopropil]‐7‐hidroksi‐3,4‐dihidro‐2H‐1,3‐benzoksazin‐2,4‐dion dan 3‐(3‐{2‐amino‐5‐okso‐5H,6H‐imidazo[4,5‐d]azepin‐4‐il}‐2‐oksopropil)‐7‐bromo‐6‐kloro‐3,4‐dihidrokuinazolin‐4‐on. Kedua senyawa ini memiliki nilai energi interaksi sebesar -10,79 kkal/mol dan -10,19 kkal/mol yang mendekati nilai dari halofuginon sebesar -10,98 kkal/mol. Selanjutnya perlu dilakukan verifikasi dengan melakukan uji in vitro terhadap enzim PRS dan parasit Plasmodium falciparum, serta uji toksisitas agar didapat turunan febrifugin yang poten dan non-toksik.