Browsing by Author "Ibrahim, Mohammed Auwal"

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    The dipeptidyl peptidase IV inhibitory activity and multifunctional antidiabetic properties of SQSPA: Structure – Activity relationship evaluated with alanine scanning
    (Elsevier, 2020-05-29) Ibrahim, Mohammed Auwal; Serem, June C.; Bester, Megan J.
    Type 2 diabetes is a multifactorial disease and drugs with multifunctional properties are required. The peptide, SQSPA, was reported to be a potent and gastrointestinally stable α-glucosidase inhibitory peptide. In this study, the structure-activity relationship of this peptide was studied using alanine scanning. Four analogs; AQSPA, SASPA, SQAPA and SQSAA were designed and investigated for multifunctional antidiabetic effects. Molec ular docking studies on human dipeptidyl peptidase-IV (DPP-IV) suggested that the binding affinities were in the order; AQSPANSASPANSQSPANSQSAANSQAPA while for in vitro DPP-IV inhibitory activity, it was SQSPANSQSAANAQSPANSASPANSQAPA. Enzyme kinetic studies revealed that the peptides are uncompetitive in hibitors with the exception of SQSAA and SQSPA. In 3T3-L1 differentiated adipocytes, SASPA was the only analog that significantly (p b 0.05) reduced and prevented lipid accumulation and did not induce cytotoxicity to differ entiated 3T3-L1 cells. All peptides, especially SASPA scavenged methylglyoxal and peroxyl radicals thereby preventing advanced glycosylated end products formation and oxidative stress. The nitric oxide scavenging activAAity of all peptides was comparable to IPI and glutathione. Findings indicate that the amide side chain of Q2 is probably the most critical functional group for modulating the multifunctional antidiabetic effects of SQSPA while SASPA has been identified, as a novel peptide with enhanced multifunctional antidiabetic
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    Eugenia uniflora and Syzygium samarangense extracts exhibit anti-trypanosomal activity: Evidence from in-silico molecular modelling, in vitro, and in vivo studies
    (Elsevier, 2021-03-20) Abdelfattah, Mohamed A.O.; Ibrahim, Mohammed Auwal; Abdullahi, Hadiza Lawal
    The parasite Trypanosoma brucei is the main cause of the sleeping sickness threatening millions of populations in many African countries. The parasitic infection is currently managed by some synthetic medications, most of them suffer limited activity spectrum and/or serious adverse effects. Some studies have pointed out the promising therapeutic potential of the plant extracts rich in polyphenols to curb down parasitic infections caused by T. brucei and other trypanosomes. In this work, the main components dominating Eugenia uniflora and Syzygium samarangense plant extracts were virtually screened, through docking, as inhibitors of seven T. brucei enzymes validated as potential drug targets. The in vitro and in vivo anti-T. brucei activities of the extracts in two treatment doses were evaluated. Moreover, the extract effects on the packed cell volume level, liver, and kidney functions were assessed. Five compounds showed strong docking and minimal binding energy to five target enzymes simultaneously and three other compounds were able to bind strongly to at least four of the target enzymes. These compounds represent lead hits to develop novel trypanocidal agents of natural origin. Both extracts showed moderate in vitro anti-trypanosomal activity. Infected animal groups treated over 5 days with the studied extracts showed an appreciable in vivo anti-trypanosomal activity and ameliorated in a dose dependent manner the anaemia, liver, and kidney damages induced by the infection. In conclusion, Eugenia uniflora and Syzygium samarangense could serve as appealing sources to treat trypanosomes infections.
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    Interaction of SARS-CoV-2 spike protein with angiotensin converting enzyme inhibitors and selected compounds from the chemical entities of biological interest
    (Springer Nature, 2021-08-25) Aminu, Suleiman; Ibrahim, Mohammed Auwal; Sallau, Abdullahi Balarabe
    Background Recent COVID-19 outbreak has prompted the search of novel therapeutic agents to treat the disease. The initial step of the infection involves the binding of the virus through the viral spike protein with the host angiotensin converting enzyme 2 (ACE2). In this study, the interaction of some ACE or ACE2 inhibitors and their analogues as well as selected compounds with the viral spike protein as a strategy to hinder viral-ACE2 interaction were investigated. SARS-CoV-2 spike protein as well as the ligands were retrieved from protein databank and ChEBI database respectively. The molecules were prepared before initiating the virtual screening using PyRx software. Discovery studio was used to further visualize the binding interactions between the compounds and the protein. Results The ACE inhibitors and their analogues fosinopril (1-), fosinopril and moexipril have the best binding affinity to the protein with binding energies < - 7.0 kcal/mol while non-flavonoid stilben-4-ol binds with free binding energy of - 7.1 kcal/mol. Others compounds which belong to either the flavonoids, terpenes and alkaloid classes also have binding energies < - 7.0 kcal/mol. Such high binding energies were enhanced via hydrogen bond (h-bond) interactions in addition to other interactions observed between the compounds and the amino acid residues of the protein. Conclusions The ACE inhibitors and their analogues as well as the selected compounds could serve as inhibitors of the spike protein as well as lead in drug discovery processes to target the SARS-CoV-2 virus.
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    The therapeutic potential of phytol towards Trypanosoma congolense infection and the inhibitory effects against trypanosomal sialidase
    (Elsevier, 2020-06-27) Saad, Saad Bello; Ibrahim, Mohammed Auwal; Jatau, Isa Danladi
    The search for novel therapeutic candidates against animal trypanosomiasis is an ongoing scientific endevour because of the negative impacts of the disease to the African livestock industry. In this study, the in vivo ther apeutic potentials of phytol toward Trypanosoma congolense infection and the inhibitory effects on trypanosomal sialidase were investigated. Rats were infected with T. congolense and administered daily oral treatment of 50 and 100 mg/kg BW of phytol. Within the first 10 days of the treatment, no antitrypanosomal activity was recorded but a moderate trypanostatic activity was observed from day 17-day 21 pi. However, at 100 mg/kg BW, phytol demonstrated a significant (p < 0.05) ameliorative potentials toward T. congolense-induced host-associated pathological damages such as anaemia, hepatic and renal damages; and the data was comparable to dimina zine aceturate. Moreover, the T. congolense caused a significant (p < 0.05) increase in free serum sialic acid level which was significantly (p < 0.05) prevented in the presence of phytol (100 mg/kg BW). In an in vitro analysis, phytol inhibited partially purified T. congolense sialidase using an uncompetitive inhibition pattern with inhi bition binding constant of 261.24 μmol/mL. Subsequently, molecular docking revealed that the compound binds to homology modelled trypanosomal sialidase with a binding free energy of