Novel terpene based 1,4,2-dioxazoles: Synthesis, characterization, molecular properties and screening against Entamoeba histolytica

• Published in: European journal of medicinal chemistry Vol. 46; no. 9; pp. 4742 - 4752
• Main Authors: Younus Wani, Mohmmad, Athar, Fareeda, Salauddin, Attar, Mohan Agarwal, Subhash, Azam, Amir, Choi, Inho, Roouf Bhat, Abdul
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 01.09.2011; Elsevier
• Subjects: Animals; Anti-amoebic activity; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Biological and medical sciences; Chemistry, Medicinal; Cytotoxicity studies; Dioxazole; Entamoeba histolytica - drug effects; Life Sciences & Biomedicine; Medical sciences; Oxazoles - chemical synthesis; Oxazoles - chemistry; Oxazoles - pharmacology; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Science & Technology; Terpene; Terpenes - chemistry; Terpene; Dioxazole; Anti-amoebic activity; Cytotoxicity studies; PLANT; PERMEABILITY; DRUG DISCOVERY; PREDICTION; ELECTROPHORESIS; ORAL BIOAVAILABILITY; RESISTANCE; ISOPRENOIDS PERILLYL ALCOHOL; DERIVATIVES; CONSTITUENTS; Heart; Five membered ring; Lobosea; Rat; Nitrogen heterocycle; Toxicity; Dissociation constant; Cytotoxicity; Harmlessness; Physicochemical properties activity relationship; Oxygen heterocycle; Antiprotozoal agent; Structure activity relation; Six membered ring; Bicyclic compound; Aromatic compound; Chemical properties; Chemical synthesis; Oxygen nitrogen heterocycle; Protozoa; Rodentia; Prediction; Entamoeba histolytica; In vitro; Vertebrata; Mammalia; Animal; Myoblast; Parasiticide; Property structure relationship; Lipophilicity; Physicochemical properties
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2011.06.005

In present investigation a series of 20 dioxazole analogues ( 1– 20) were synthesized, characterized and subjected to molecular properties prediction, anti-amoebic screening and cytotoxicity evaluation. Out of the twenty compounds viz. 3,5-substituted-1,4,2-dioxazoles, six compounds have shown IC 50 values in the range (1.00–1.10 μM) lower than the standard drug metronidazole (IC 50 = 1.45 μM). The toxicological studies of the active compounds on H9c2 rat cardiac myoblasts showed that all compounds were nontoxic. The pKa, and log P values have also been predicted. Compound 8 showed the most promising results based on anti-amoebic evaluation, cytotoxicity studies and physico-chemical properties prediction. A series of 20 dioxazole derivatives were synthesized and screened against Entamoeba histolytica, compound 8 obeying Lipinski’s “Rule of Five” shows higher growth inhibition and least toxicity. [Display omitted] ► Synthesis of new series of terpene based 1,4,2-dioxazoles. ► The compounds with consideration of Lipinski’s “Rule of Five”. ► Molecular properties were determined using the bio-informatics tools. ► The molecules were screened in vitro for Entamoeba histolytica, and cytotoxic effects.