101-88-2Relevant articles and documents
New isoleucine derived dipeptides as antiprotozoal agent: Synthesis, in silico and in vivo studies.
Ekoh, Ogechi C.,Okoro, Uchechukwu C.,Ali, Rafat,Ugwu, David I.,Okafor, Sunday N.,Ezugwu, James A.
, (2021)
The increasing emergence of malaria drug-resistant parasites and the deficiency in effective chemotherapy for trypanosomiasis represents a huge challenge in infectious disease treatment in tropical regions. As regards to developing effective antiprotozoal agents, ten new ile-gly dipeptide sulphonamide derivatives were synthesized by condensing compound (10) with (8a-j)using peptide coupling reagents. Compounds11b, 11i and 11j were most potent in clearing Trypanosome brucei in mice with 11b showing comparable activity with diminazene aceturate. In the antimalarial study, 11b was the most active compound, even better than the standard. Molecular docking result suggests good interaction between the reported compounds and the target protein. The results of haematological analysis, liver and kidney function tests showed that the compounds had no adverse effect on the blood and organs. Compound 11b stands out amongst the derivatives haven shown better activity in both the antimalarial and antitrypanosomal assay.
New glycine derived peptides bearing benzenesulphonamide as an antiplasmodial agent
Ugwuja, Daniel Izuchukwu,Okoro, Uchechukwu,Soman, Shubhanji,Ibezim, Akachukwu,Ugwu, David,Soni, Rina,Obi, Bonaventure,Ezugwu, James,Ekoh, Ogechi
, p. 3660 - 3674 (2021/03/03)
In the tropics, malaria is among the most serious infectious diseases in developing countries. The discovery of the artemesinin antimalarial drug not too long ago was a major breakthrough in the effort to combat the malaria disease. However, recent reports of resistance even to combination therapy involving artemisinin are very worrisome and have led to the search for new chemical agents to sustain the fight against malaria. The carboxamide functionality has been shown to be an important pharmacophore in over 25% of commercial chemotherapeutic agents. Three benzensulphonamides (3a-c) were prepared from the reaction of the appropriate benzensulphonyl chloride (1a-c) and alanine (2) in aqueous basic medium. Eight tert-butylamino-oxo-ethylcarbamates (5a-h) were also prepared from reacting commercially available boc-glycine (4) and different amines using peptide coupling reagents such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and 1-hydroxybenzotriazole (HOBt), with triethyl amine and dichloromethane (DCM) as solvents. The target compounds were prepared by reacting compounds 3a-c with compounds 5a-h in the presence of coupling reagents to get twenty four (24) different compounds. The compounds were characterized and evaluated for their antiplasmodial activity. Computed molecular descriptors and assessed biochemical parameters showed that the compounds were drug-like and safe. All the compounds had favourable binding interactions with residues at the PABA binding site of homologically modeled P. falciparum dihydropteroate synthase and henceforward the in vitro and in vivo antiplasmodial activities were evaluated. Compounds 7a-7x showed activity against P. falciparum (W2 strain) at MIC values ranging from 3.52 to 0.09 μM. Moreover, seven of the compounds (7c, 7d, 7i, 7j, 7p, 7r and 7s) showed better activity than quinine (MIC = 0.72 μM). In addition, 16 of the 24 compounds were found to clear more than 50 percent of P. berghei (NK-65 strain) from the blood of infected mice at 12 days post-infection. The percentages of parasites cleared by 20 mg kg-1 of the three most effective compounds (7g, 7n and 7r) were 74.98, 74.98 and 74.07, respectively. In conclusion, 7r (MIC 0.71 μM) from this class of glycine derived sulfonamides has the ability to clear 74.07% of P. berghei from blood of infected mice at 20 mg kg-1 and an interesting pharmacokinetic profile (MW = 430.31 Da, HBA = 7, HBD = 3, log?P = 2.56, NRB = 9 and TPSA = 104.37 ?2), which is in agreement with the Lipinski rule of 5 for a compound to be qualified as a drug candidate. 7r could serve as a lead in developing new antiplasmodial agents. This journal is
New peptide derived antimalaria and antimicrobial agents bearing sulphonamide moiety
Ugwuja,Okoro,Soman,Soni,Okafor,Ugwu
, p. 1388 - 1399 (2019/08/22)
Fourteen novel dipeptide carboxamide derivatives bearing benzensulphonamoyl propanamide were synthesized and characterized using 1H NMR, 13C NMR, FTIR and MS spectroscopic techniques. In vivo antimalarial and in vitro antimicrobial studies were carried out on these synthesized compounds. Molecular docking, haematological analysis, liver and kidney function tests were also evaluated to assess the effect of the compounds on the organs. At 200 mg/kg body weight, 7i inhibited the multiplication of the parasite by 81.38% on day 12 of post-treatment exposure. This was comparable to the 82.34% reduction with artemisinin. The minimum inhibitory concentration (MIC) in μM ranged from 0.03 to 2.34 with 7h having MIC of 0.03 μM against Plasmodium falciparium. The in vitro antibacterial activity of the compounds against some clinically isolated bacteria strains showed varied activities with some of the new compounds showing better activities against the bacteria and the fungi more than the reference drug ciprofloxacin and fluconazole.
