Semi-Synthesis and Cytotoxicity Evaluation of Pyrimidine, Thiazole, and Indole Analogues of Argentatins A–C from Guayule (Parthenium Argentatum) Resin

Argentatins A–C (1–3), the major cycloartane-type triterpenoids of guayule resin, a byproduct of commercial rubber production, were converted into their pyrimidine (7–12), thiazole (13–15), and indole (16–18) analogues by a molecular hybridization approach. The cytotoxic activities of these fused heterocyclic analogues 7–18 were compared with those of argentatins A–C (1–3) against a panel of three sentinel human cancer cell lines [NCI-H460 (non-small cell lung), MCF-7 (breast adenocarcinoma), and SF-268 (central nervous system glioma)], and normal human fibroblast (WI-38) cells. The cytotoxicity data suggest that the pyrimidine analogues 7 and 8 (derived from 1), 9 and 10 (derived from 2), and 12 (derived from 3 ) had significantly enhanced activity compared to the parent compounds or their thiazole (13–15) and indole (16–18) analogues. These findings indicate that triterpenoid constituents of guayule resin may be exploited to obtain value-added products with potential applications in anticancer drug discovery.

Acetyleugenol from Acacia nilotica (L.) Exhibits a Strong Antibacterial Activity and Its Phenyl and Indole Analogues Show a Promising Anti-TB Potential Targeting PknE/B Protein Kinases

Acetyleugenol is a phytochemical compound with broad effects against infectious diseases and tumors. Here, we extracted, characterized, and elucidated the structure of acetyeugenol, for the first time, from the leaves of Acacia nilotica (L.)—a well-known medicinal plant. The broad antibacterial potential of acetyleugenol was first confirmed against seven bacterial clinical isolates, which reveal a strong activity against Proteus sp., Salmonella typhi, Staphylococcus aureus, and Streptococcus pneumonia with similar or better zone of inhibition comparing to that of the control amoxicillin. To further investigate its effect against Mycobacterium tuberculosis, acetyleugenol and its indole and phenyl analogues were subjected to molecular docking experiments against two potential tuberculosis drug targets—MtPknE and MtPknB Ser/Thr protein kinases. The results reveal that all of the analogs have improved docking scores compared to the acetyleugenol. The indole analogues EUG-1 and EUG-3 were more effective with better docking scores for MtPknE with −11.08 and −10.05 kcal/mol, respectively. Similar results were obtained for the MtPknB. In contrast, only the EUG-2 phenyl analogue has given rise to similar docking scores for both targets. This opens the door for further comprehensive studies on these acetyleugenol analogues with in vitro and in vivo experiments to validate and get more insights into their mechanisms of action.

Synthesis of Biologically Active Novel Indole Fused Heterocyclic Derivatives: Molecular Modeling Studies

A novel series of fluoro/methoxy indole analogues 6 was synthesized and the final targets were confirmed by IR, 1H & 13C NMR and mass spectral analysis. Novel 3-substituted indole derivatives estimate for their antibacterial, antioxidant activities particularly the parent core combined with benzamides ring significantly. From antibacterial activities, compounds 6c, 6e and 6b show the highest bacterial activity against S. epidermidis, S. aureus, E. coli, with zone of inhibition 34, 30, 28 mm, respectively. Novel fluoroindole derivatives 6c, 6b, 6i shows an excellent antioxidant activity with % of inhibition 150.12, 139.04, 137.08 mmol/mL, respectively. The calculations for ligand-protein flexible of crystal structure of C(30) carotenoid dehydrosqualene synthase from S. aureus complexed with bisphosphonate BPH-700 (2ZCS). Among the designed compounds 6c exhibited highest hydrogen bonding interactions 2.06 Å, 1.85 Å with amino acids Asp27, Lys273 and binding energy -6.38 kcal/ mol, respectively. Fluoroindoles 6i, 6e and 6f shows highest ΔG = -7.90, -7.66, -7.47 kcal/mol with dissociation constants 10.32, 21.77, 22.68 μM and amino acid Lys273 interactions.