Recent publications
Background Cancer is a major health threat especially in unindustrialized nations. It surpasses coronary diseases and takes the number one killer position as a result of different global wide influences. Among many breast cancer substrates, triple-negative breast cancer (TNBC) is particularly devastating because it rapidly metastasize to other parts of the body, with a high risk of earlier recession and mortality. Result In this research work, four (4) quantitative structure activity relationship (QSAR) models were developed using a series of quinazoline derivatives with activities against triple negative breast cancer cell line (MDA-MB231), model 1 was selected due to its statistical fitness with the following validation parameters: R ² = 0.875, Q ² = 0.837, R ² − Q ² = 0.038, N ext test set = 5, and R ² ext = 0.655. Molecular docking studies was performed for the quinazoline series as well as the reference drug (Gefitinib) and the active site of the epidermal growth factor receptor (EGFR) (pdb id = 3ug2). Eight compounds (6, 10, 13, 16, 17, 18, 19 and 20) were observed to have better docking score docking scores relative to Gefitinib. Compound number nineteen from the training set (pred pIC 50 = 5.67, Residual = − 0.04 and MolDock score = − 123.238) was identified as the best compound since it has the best Moldock score and was excellently predicted by the selected model with least residual value, Hence was adopted as template for the design of Ten (10) new novel compounds with better activities and better docking scores. The inhibitive activities of the designed compounds were predicted by the selected model and most of them possess an improved activity relative to the template compound (19). The designed compounds were also redocked on to active pocket of the EGFR receptor and it was observed that they displayed better docking scores compared to the Template and the reference drug (Gefitinib) utilized in the design. Furthermore, the designed compounds were subjected to ADMET and drug-likeness studies using SWISSADME and pkCSM online web tools and they were observed to be pharmacologically active, easily synthesized and do not violate the Lipinski’s rule of five. Conclusion Hence, the designed compounds can be employed as inhibitors of MDA-MB231 cell line after passing through in vivo and in vitro evaluation.
The sole aim of this article is to examine the relative contribution of suction/injection parameter on Taylor–Dean flow in a composite annular gap partially filled with porous material. In the present setup, the Newtonian fluid flow is induced by the circumferential motion of both cylinders and pressure gradient imposed in the Azimuthal direction. The mathematical model governing the flow is rendered dimensionless using appropriate dimensionless quantities transformed using the Laplace transform technique. Using suitable Ansatz, the equation is reduced to the Bessel differential equations and solved. The solution of converted to the time domain using a well-known numerical scheme known as the Riemann-sum approximation. The variation of the Newtonian fluid for different flow parameters is presented graphically. The solution method is validated by obtaining the steady-state solution and also using the implicit finite different approach (IFD); comparison of the methods is depicted in tabular form (see Tables 1, 2). It is deduced generally that the Newtonian fluid is higher when injection at the outer cylinder except when Da is small also higher interfacial velocity can be achieved by taking positive value of $$\beta$$ β .
Environmental contamination with Cr (VI) has recently attracted public attention because of its high concentration in soil and wastewater originating majorly from anthropogenic activities and natural processes. Reduction of Cr (VI) to Cr (III) is a feasible method for minimizing chromium pollution. This work aimed at characterizing the effects of Cr (VI) reduction conditions in a batch experiment such as temperature, hydrogen ion concentration, time, and reactant concentrations, as well as kinetics and thermodynamics of the reaction using Tamarindus indica methanol leaves extract as a reductant. Cr (VI) reduction was meaningfully affected by temperature, hydrogen ion concentration, reaction time, and reactant concentrations. The reaction followed the pseudo-second-order kinetic model ( R ² = 0.997) at pH of 2; at the neutral and alkaline pH (7 and 9), the reaction predominantly obeyed first order ( R ² = 0.988) and pseudo-first order ( R ² = 0.758), respectively. Under various hydrogen ion concentrations, the reaction retains negative free energies, enthalpy change, and a positive entropy. The findings from this study suggested the reaction to be spontaneous, exothermic, and orderly unstable. We concluded that phytocompounds present in tamarind methanol leaves extract demonstrated a strong potentials for converting Cr (VI) to Cr (III) and, thus, could be applicable in Cr (VI) contaminated wastewater treatment.
Background Alzheimer's disease (AD) is a multifactorial disorder that gradually destroys wisdom and memory skills. Currently, this disease can only be treated palliatively. However, the molecular mechanisms underlying this condition remain elusive. Therefore, these treatments are inadequate. Current medications can only increase patient warning signs. Chemical structures were drawn using Chemsketch software. Spartan’14 software was used to optimize the structures using density functional theory (DFT). The PaDEL software was used to generate the descriptors. The genetic function algorithm (GFA) and multi-linear regression (MLR) approaches were used to generate the QSAR model. Results In the present study, we performed a computational investigation, molecular docking, and pharmacokinetics analysis of 1,3-dimethylbenzimidazolinone derivatives. The descriptors generated in the model are AATS7i, MATS5p, SpMin7_Bhe, and GATS6c. Compounds 13 and 21 have the best binding scores, 11.2 kcal/mol and 10.8 kcal/mol, respectively, and optimal protein–ligand interactions with AChE. These compounds have brilliant pharmacokinetic and physicochemical properties. Conclusions The model was validated and found to have good internal and external assessment parameters: R ² = 0.937, $$R_{{{\text{adj}}}}^{2}$$ R adj 2 = 0.863, $$Q_{{{\text{cv}}}}^{2}$$ Q cv 2 = 0.788, $$R_{{{\text{test}}}}^{2}$$ R test 2 = 0.756, LOF = 0.0268, $$cR_{{\text{p}}}^{2}$$ c R p 2 = 0.677. In summary, these data suggested that compounds 13 and 21 are promising multifunctional agents against AD.
Background Hepatitis C virus (HCV) is a contagious disease that damages the liver over time, eventually leading to cirrhosis and death. Chronic HCV infection is regarded as a serious health problem worldwide, impacting up to 3% of the populace and killing over 300,000 people annually. Quick reproduction driven by non-structural protein 5B (NS5B), which is a possible target spot for the development of anti-HCV vaccines, causes genomic diversity. Sofosbuvir, a new oral NS5B inhibitor, was recently licensed by the US Food and Drug Administration for the cure of HCV. Unfortunately, it has received a lot of attention due to its financial concerns and adverse effects. As a result, there is a pressing need to explore alternative HCV treatments that are both cost-effective and free of adverse effects. In this study, we used a Pharmacoinformatics-based strategy to identify and design bioactive molecules that are anti-HCV NS5B. The simulation outcomes are compared to Sofosbuvir simulation outcomes. Results Based on docking simulation, the proposed molecules have high-binding energies at the range of − 41.71 to − 39.90 kcal/mol against − 30.34 kcal/mol of Sofosbuvir. Furthermore, when compared to Sofosbuvir, which has a drug score of 0.31 (31% performance), the ADMET analysis of the lead compound demonstrates superior performance with a drug score of 0.88 (88% performance). Conclusions The findings revealed that alternative bioactive molecules vary substantially in docking rankings at a range of − 41.71 to − 39.90 kcal/mol against − 30.34 kcal/mol of Sofosbuvir, the FDA-approved NS5B enzyme inhibitor, and when compared to Sofosbuvir, which has a drug score of 0.31, the ADMET analysis of the chosen compound ( 1c ) demonstrates superior performance with a drug score of 0.88.
Background The study of Piszkiewicz’s and Berezin’s models on the redox reaction of allylthiourea and bis-(2-pyridinealdoximato)dioxomolybdate(IV) complex ([Mo IV O 2 (paoH) 2 ] ²⁻ ) in an aqueous acidic medium is suggested. The Piszkiewicz’s and Berezin’s models are applied, and their parameters are used to explain the redox behaviour of allylthiourea with Mo(IV) complex in the presence of surfactants. Results The reaction followed a high cooperativity pattern that reflects a strong interaction between the two redox partners in the presence of cetyltrimethylammonium bromide (CTAB) which is reinforced by a notable binding constant at the Stern layer of the micelle. The effect of cationic counter-ion (Ca ²⁺ ) on the reaction rate further confirmed the effectiveness of the interaction at the rate-limiting step. The presence of sodium dodecyl sulphate (SDS) in the reaction medium resulted in reaction inhibition which reveals the interplay of electrostatic repulsion at the electrophilic polar head of the surfactant and the redox species. The effect of ionic strength on the reaction rate shows that one of the reacting species is not charged (neutral) which kept the rate of the reaction uniform at different salt concentrations studied. The change in the medium polarity buttressed the effect of ionic strength on the reaction which is explained better by Piszkiewicz’s and Berezin’s models. Free radical was actively engaged in the reductive process of the Mo(IV) complex, and this revealed that the hydrophobic region is a possible location for the interaction of the redox partner in the presence of SDS micelle. Conclusions The models depict well the microenvironments of enzymatic reactions involving bimolecular interactions with significant binding constants and cooperativity indexes that show the strength of the interaction between the substrates and surfactant molecules. Graphical Abstract
Background Preparation of Ipomoea asarifolia (Desr) (Convolvulaceae) is widely used in traditional African medicine for the treatments of different kinds of ailments such as syphilis, malaria, convulsions and rheumatism. Aim The anticonvulsant properties of fractions of leaf of Ipomoea asarifolia (Desr); n -butanol (BF), chloroform, n -hexane and residual aqueous fractions (RAF) were evaluated on animals. Results The RAF at dose of 75 mg/kg ( P < 0.01) with 33% quantal protection and 83% protection against mortality is the most active fraction when compared with BF at 300 mg/kg ( P < 0.01) with no quantal protection and 83% protection against mortality; the anti-seizure activity could be because of the presence of saponins (23.3%) and flavonoids (43.92%). The RAF may also owes its anticonvulsant activity via GABAergic pathway as flumazenil at 2 mg/kg significantly ( P < 0.05) blocked the activity of RAF, via glutamatergic pathway with RAF ( P < 0.05) significantly reversing the proconvulsive activity of ketamine at 200 mg/kg as compared to ketamine alone. Opioidergic pathway may also be implicated as naloxone 1 mg/kg significantly ( P < 0.05) reduced the anticonvulsant effect of RAF. Conclusions BF and RAF of leaf of Ipomoea asarifolia have shown anticonvulsants activities in PTZ-induced seizures. RAF was observed to be the most active fraction of Ipomoea asarifolia extract which probably exerts its action through GABAergic, glutamatergic and opioidergic pathways.
Background Alzheimer disease (AD) is an ailment that disturbs mainly people of old age. The fundamental remedial way to deal with AD depends on the utilization of AChEI. The design of new intense and particular AChEI is critical in drug discovery. In silico technique will be used to solve the above problem. A new method was established to discover novel agents with better biological activity against Alzheimer disease. Results A validated model was established in this research to predict the biological activities of some anti-Alzheimer compounds and to design new hypothetical drugs influenced with molecular properties in the derived model; ATS4i, MATS2e, SpMax7_BhS, Energy (HOMO) and Molecular Weight and showed good correlation R ² = 0.936, R ² adj = 0.907, Q ² cv = 0.88, LOF = 0.0154 and R ² ext = 0.881. All the descriptors in the model were in good agreement with the 15 test set predicted values. Five compounds were designed using D35rm as a template with improved activity. The compounds have higher and better binding scores (− 10.1, − 9.4, − 9.3, − 9.1 and − 8.1 all in kcal/mol) than the approved drugs (Donepezil = − 7.4 kcal/mol). Conclusion As the outcome, every one of the selected and the designed compounds is created and improved as potential anti-Alzheimer agents. Despite this, the further test examines and in vivo investigations are recommended to assess the method of the activities and other pharmacological impacts on these compounds.
Background Diabetes mellitus (DM) is one of the most defying health risk in the twenty-first century promoting a high rate of morbidity and mortality that could possibly increase if no intervention is in place. However, drugs for curing DM are available but are associated with adverse side effect necessitating the pursuit for a safe antidiabetic drugs. The present study was conducted in order to develop a QSAR model that would be used to predict the activities of salicylic acid derivatives, as well as to determine the binding interactions of the compounds with α-glucosidase using molecular docking studies. Results Model one was selected and reported as the best model based on its fitness with the following validation keys: R ² (trng set) = 0.968, R ² (adj) = 0.957, Q ² (cv) = 0.932, LOF = 0.085 and R ² (test set) = 0.864. Five potent analogues were designed using the ligand-based method with their predicted activities been calculated and found to be higher compared to the lead compound. Furthermore, binding interactions of the designed analogues within the active site of α -glucosidase (pdb id:3L4V) illustrate a good binding affinities than kotalanol and acarbose. However, the ADMET and drug-likeness properties predicted the design analogues to be pharmacologically and orally safe by not having more than one violation of Lipinski’s (Ro5) criteria. Conclusions The present findings therefore showed that the salicylic acid derivatives could serve as α -glucosidase inhibitors. The compounds can be studied further for a hunts of promising drug candidates against diabetes mellitus.
Background Coumarin and fatty alcohol are abundant in nature, particularly in plants, and have been reported to have therapeutic uses. Strychnos innocua ( Loganiaceae family) is commonly utilized for medicinal purposes in several African countries. Ethyl acetate extract of the plant (root bark) was subjected to chromatography separation, leading to the isolation of Umbelliferone ( 1 ) and 2,13-octadecadien-1-ol ( 2 ). Results Their structures were verified using mass spectrometry (MS) and nuclear magnetic resonance (NMR) and then compared with published data. This is the first time these compounds ( 1 and 2 ) have been isolated from S. innocua root bark. In the molecular docking analysis, the binding scores of the compounds ( 1 and 2 ) with the binding sites of Staphylococcus aureus pyruvate carboxylase (PDB: 3HO8) and Pseudomonas aeruginosa virulence factor regulator (PDB: 2OZ6) were − 5.6 and − 4.7 kcal/mol, and − 6.9 and − 5.7 kcal/mol, respectively. These were compared with ciprofloxacin (standard drug), which had docking scores of -6.6 and -8.7 kcal/mol, respectively. Conclusions In conclusion, this study established the rich presence of Umbelliferone and 2,13-octadecadien-1-ol in the plant root bark, and their docking studies revealed moderate binding potential with the binding sites of S . aureus and P . aeruginosa . Graphical Abstract
Background In spite of the significant escalation in the depth of our conception and regulation of breast cancer over the past decades, the malady is still a serious community health challenge globally and poses a substantial tasks. Selective estrogen modulators (SERMs) such as Tamoxifen are approved for the therapy of this illness but developed drug resistance and unwanted side effects such as endometrial cancer caused by the long-term Tamoxifen chemotherapy limit their therapeutic applicability. Hence, developing new ER ⁺ drugs with better therapeutic effect is strongly needed. In an attempt to overcome this challenge, this research is aimed at designing novel chromen-2-one analogues with better inhibition capacity against MCF-7 breast cancer cell line via structural modification of the reference compound and predict their activities using a developed QSAR model. Results Four models were developed, and the first was selected for the design as it has the highest statistical parameters such as: coefficient of determination ( R ² = 0.950), cross-validation coefficient ( Q cv ² = 0.912), adjusted R ² ( R adj ² = 0.935), and external validation R ² ( R pred ² = 0.7485). Twelve (12) new novel chromen-2-one analogs were designed through structural modification of the reference compound. Their activities was predicted using the selected model, and their pIC 50 was found to be better than that of the reference compound and standard drug (Tamoxifen) used in the research. Results of pharmacokinetic study of the designed compounds revealed that they possess drug-likeness properties as none of them violated the Lipinski’s rule of five while ADMET studies confirmed designed compounds 6, 8, 11 and 12 as orally safe and non-toxic. Furthermore, molecular docking analysis was performed between these orally safe designed compounds and the active site of the ER ⁺ receptor and the result showed that they have higher binding affinities than the reference compound and the standard drug used for this research. Conclusion Hence, designed compounds 6, 8, 11 and 12 can be used as novel ER ⁺ breast cancer drug candidates after performing in vivo and in vitro studies.
Background In 2003, the first case of severe acute respiratory syndrome coronavirus (SARS-CoV) was recorded. Coronaviruses (CoVs) have caused a major outbreak of human fatal pneumonia. Currently, there is no specific drug or treatment for diseases caused by SARS CoV 2. Computational approach that adopts dynamic models is widely accepted as indispensable tool in drug design but yet to be exploited in covid-19 in Zaria, Nigeria. In this study, steps were taken to advance on the successful achievements in the field of covid-19 drug, with the aid of in silico drug design technique, to create novel inhibitor drug candidates with better activity. In this study, one thousand human immunodeficiency virus (HIV1) antiviral chemical compounds from www.bindingBD.org were docked on the SARS CoV 2 main protease protein data bank identification number 6XBH (PDB ID: 6XBH) and the molecular docking score were ranked in order to identify the compounds with the highest inhibitory effects, and easy selection for future studies. Results The docking studies showed some interesting results. Inhibitors with Index numbers 331, 741, and 819 had the highest binding affinity. Similarly, inhibitors with Index number 441, 847, and 46 had the lowest hydrogen bond energy. Inhibitor with index number 331 was reported with the lowest value (− 48.38kCal/mol). Five new compounds were designed from the selected six (6) compounds with the best binding score giving a total of thirty (30) novel compounds. The low binding energy of inhibitor with index no. 847b is unique, as most of the interaction energies are of H-bond type with amino acids (Thr26, Gly143, Ser144, Cys145, Glu166, Gln189, Hie164, Met49, Thr26, Thr25, Thr190, Asn142, Met165) resulting in an overall negative value (−16.31 kCal/mol) making it the best of all the newly designed inhibitors. Conclusions The novel inhibitor is 2-(2-(5-amino-2-((((3-aminobenzyl)oxy)carbonyl)amino)-5-oxopentanamido)-4-(2-(tert-butyl)-4-oxo-4-(pentan-3-ylamino) butanamido)-3-hydroxybutyl) benzoic acid. The improvement it has over the parent inhibitor is from the primary amine group attached to meta position of first benzene ring and the carboxyl group attached to the ortho position of the second benzene ring. The molecular dynamics studies also show that the novel inhibitor remains stable after the study. This result makes it a better drug candidate against SARS CoV 2 main protease when compared with the co-crystallized inhibitor or any of the 1000 docked inhibitors.
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