Design, Synthesis, and Biological Evaluation of New 1-(Aryl-1H-pyrrolyl)(phenyl)methyl-1H-imidazole Derivatives as Antiprotozoal Agents

Abstract

We have designed and synthesized a series of new imidazole-based compounds structurally related to an antiprotozoal agent with nanomolar activity which we identified recently. The new analogues possess micromolar activities against Trypanosoma brucei rhodesiense and Leishmania donovani and nanomolar potency against Plasmodium falciparum. Most of the analogues displayed IC50 within the low nanomolar range against Trypanosoma cruzi, with very high selectivity toward the parasite. Discussion of structure–activity relationships and in vitro biological data for the new compounds are provided against a number of different protozoa. The mechanism of action for the most potent derivatives (5i, 6a–c, and 8b) was assessed by a target-based assay using recombinant T. cruzi CYP51. Bioavailability and efficacy of selected hits were assessed in a T. cruzi mouse model, where 6a and 6b reduced parasitemia in animals >99% following intraperitoneal administration of 25 mg/kg/day dose for 4 consecutive days.

Recent Advances in Recovery of Lycopene from Tomato Waste: A Potent Antioxidant with Endless Benefits

“…Lycopene is a phytonutrient playing an important role in human health. Indeed, it has long been known for its several biological activities such as antioxidant [ 10 ], anti-inflammation [ 11 ], hypoglycemic [ 12 , 13 ], photoprotection [ 14 ], anti-angiogenesis [ 15 ], anti-parasitic [ 16 , 17 , 18 , 19 ], antiviral [ 20 ] and others. Several studies have also indicated the effect of dietary lycopene in reducing the risk of chronic diseases such as coronary heart disease [ 21 ], being also useful in reducing the oxidative stress in human immunodeficiency virus (HIV)-infected patients under antiretroviral therapy that have less total antioxidant capacity [ 22 , 23 , 24 ].…”

Imidazole as a Promising Medicinal Scaffold: Current Status and Future Direction

“…However, compound M26 was three times more powerful than the reference drug Chloroquine (CHQ) as well as it possessed high selectivity index (SI = 253) that demonstrated the best anti-plasmodial activity. 36 …”

“… 37 Furthermore, compound M26 exhibited the highest bioactivity against all the investigated targets, one of which is enzymes (a score of 0.6) that is consistent with Saccoliti et al study which mentioned the compound works by inhibiting the CYP51 enzyme as a possible mechanism of action. 36 …”

[3+2] Anionic Cycloaddition of Isocyanides to Acyclic Enamines and Enaminones: A New, Simple, and Convenient Method for the Synthesis of 2,4‐Disubstituted Pyrroles

“…Substituted pyrroles are an interesting class of heterocyclic compounds due to their widespread use both in medical chemistry, and in the chemistry of new materials . For example, 1‐alkyl‐2‐aryl‐4‐(naphthoyl)pyrroles show high affinity for the cannabinoid receptors CB1 and CB2 (JWH series) and 1 H ‐2‐aryl‐4‐aroylpyrroles were used in the synthesis of potential antiprotozoal agents with high biological activity. In addition, pyrroles with an unsubstituted α‐position can be used in the synthesis of BODIPY, which are used in photodynamic therapy of cancer and also in other various fields of organic electronics (Figure ).…”