In Cameroon herbs are traditionally used to meet health care needs and plans on the way integrate traditional medicine in system, even though have not been put into action yet. The country however has a rich biodiversity, with ~8,620 plant species, some of which commonly treatment several microbial infections range diseases (malaria, trypanosomiasis, leishmaniasis, diabetes tuberculosis). Our survey consisted collecting published data from literature sources, mainly PhD theses Cameroonian...

Computer-aided drug design (CADD) often involves virtual screening (VS) of large compound datasets and the availability such is vital for discovery protocols. We present CamMedNP - a new database beginning with more than 2,500 compounds natural origin, along some their derivatives which were obtained through hemisynthesis. These are pure have been previously isolated characterized using modern spectroscopic methods published by several research teams spread across Cameroon. In study, 224...

We assess the medicinal value and "drug-likeness" of ∼3200 compounds natural origin, along with some their derivatives which were obtained through hemisynthesis. In present study, 376 distinct plant species belonging to 79 families from Central African flora have been considered, based on data retrieved literature sources. For each compound, optimised 3D structure has used calculate physicochemical properties determine oral availability basis Lipinski's "Rule Five". A comparative analysis...

This study aims to design improved inhibitors targeting the thymidylate kinase (TMK) of Mycobacterium tuberculosis (Mtb), causative agent infectious disease that is associated with high morbidity and mortality in developing countries. TMK an essential enzyme for synthesis bacterial DNA. We have performed computer-aided molecular MtbTMK by modification reference crystal structures lead micromolar inhibitor TKI1...

We investigated the inhibitory potency of aryloxyacetic acid derivatives (AADs) on 4-hydroxyphenylpyruvate dioxygenase (HPPD), a crucial enzyme target for HPPD herbicide development. Developing wide-ranging approach combining reported structure-activity relationships (SARs with observed potencies Kiexp), our simulations molecular mechanics Poisson-Boltzmann (MM-PB) complexation quantitative SAR (QSAR) (computed relative Gibbs free energies HPPD-AADx complex formation ΔΔGcom), and...

Drug metabolism and pharmacokinetic (DMPK) assessment has come to occupy a place of interest during the early stages drug discovery today. Computer-based methods are slowly gaining ground in this area often used as initial tools eliminate compounds likely present uninteresting profiles unacceptable levels toxicity from list potential candidates, hence cutting down cost drug. In study, we an silico DMPK profile our recently published natural products database 1,859 unique derived 224 species...

Recently, the search for new drugs against tuberculosis (TB) has been a hot topic and inhibitors validated drug targets pathways other than those currently targeted by known is suggested to be most promising way forward. Mycobacterium pantothenate synthetase (MTBPS) happens one of such targets. In quest carry out virtual screening active MTBPS get ideas design this target, we have docked set pyrazole-based site enzyme. The docking solutions were post processed using MM-PB(GB)SA method...

Cost-effective therapy of neglected and tropical diseases such as malaria requires everlasting drug discovery efforts due to the rapidly emerging resistance plasmodium parasite. We have carried out computational design new inhibitors enoyl-acyl carrier protein reductase (ENR) Plasmodium falciparum (PfENR) using computer-aided combinatorial pharmacophore-based molecular design. The Molecular Mechanics Poisson-Boltzmann Surface Area (MM-PBSA) complexation QSAR model was developed for...

We have carried out a computational structure-based design of new potent pyrrolidine carboxamide (PCAMs) inhibitors enoyl-acyl carrier protein reductase (InhA) Mycobacterium tuberculosis (MTb). Three-dimensional (3D) models InhA-PCAMx complexes were prepared by in situ modification the crystal structure InhA-PCAM1 (Protein Data Bank (PDB) entry code: 4U0J), reference compound training set 20 PCAMs with known experimental inhibitory potencies (IC50exp). First, we built gas phase quantitative...

Plasmepsin II (PlmII), an aspartic protease expressed in the food vacuole of Plasmodium falciparum ( pf ), cleaves hemoglobin host during erythrocytic stage parasite life cycle. Various peptidomimetic inhibitors PlmII reported so far discriminate poorly between drug target and proteases organism, e.g., human cathepsin D h CatD). CatD is a protein digestion enzyme signaling molecule involved variety physiological processes; therefore, inhibition by may lead to pathophysiological conditions....

We have studied inhibition of Plasmodium falciparum lactate dehydrogenase (pfLDH) by dihydroxynaphthoic acid (DHNA) analogues derivatives hemigossypol-sesquiterpene found in cottonseed known to exhibit antimalarial activity. Molecular models pfLDH-DHNA complexes were prepared from high-resolution crystal structures containing DHNA and azole inhibitors binding affinities the computed molecular mechanics - polarizable continuum model solvation (MM-PCM) approach. The 3D validated a QSAR model,...

Abstract We report here new chemical structures of predicted nanomolar triclosan‐based inhibitors (TCLs) Mycobacterium tuberculosis enoyl‐acyl carrier protein reductase (InhA) virtually proposed by computer‐assisted molecular design. 3D models InhA‐TCL complexes were prepared in situ modifications the reference crystal structure (PDB entry 1P45) for a training set 15 TCLs with known InhA inhibitory activities. A QSAR model was built leading to linear correlation between calculated free...

We design here new nanomolar antituberculotics, inhibitors of Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt), by means structure-based molecular design. 3D models TMPKmt-inhibitor complexes have been prepared from the crystal structure TMPKmt cocrystallized with natural substrate deoxythymidine (dTMP) (1GSI) for a training set 15 analogues (TMDs) known activity to prepare QSAR model interaction establishing correlation between free energy complexation and biological...

We have designed new potent inhibitors of thymidine monophosphate kinase <italic>Mycobacterium tuberculosis</italic> (TMPK_mt) using structure-based molecular design.

We report here the design of new inhibitors against human monoamine oxidase (hMAO-B) as potential treatment Parkinson’s disease. have completed computer-aided molecular MAO-B by In situ modification reference crystal structure 7-(3-chlorobenzyloxy)-4-(methylamino) methyl-coumarin cocrystallized (COU1) in complex with (Protein Data Bank (PDB) entry code: 2v61) using MM-PB approach. A QSAR model built for a training set 29 COUs reported inhibitory activities (IC50exp) displayed significant...

We report computer-aided design of new lactone–chalcone and isatin–chalcone (HLCIC) inhibitors the falcipain-2 (PfFP-2). 3D models 15 FP-2:HLCIC1-15 complexes with known observed activity (IC50exp) were prepared to establish a quantitative structure–activity (QSAR) model linear correlation between relative Gibbs free energy enzyme:inhibitor complex formation (ΔΔGcom) IC50exp: pIC50exp = −0.0236 × ΔΔGcom+5.082(#); R2 0.93. A pharmacophore (PH4) derived from QSAR directed our effort novel...

We have carried out computational optimization of antiparasitic azadipeptide nitrile inhibitors (AZN) falcipain-3 (FP3) Plasmodium falciparum (Pf), a cysteine protease the papain superfamily, using structurebased drug design and computer-assisted combinatorial chemistry.Three-dimensional (3D) models complexes inhibitor -FP3 for training sets published AZN analogs with experimentally determined inhibitory potencies were prepared by in situ modification crystal structure PfFP3 inhibited K11017...

data bank; QSAR, quantitative structure activity relationships; ΔΔG com , relative gibbs free energy change related to the enzyme-inhibitor complex formation; ΔΔH MM enthalpic contribution Gibbs derived by molecular mechanics; ΔΔTS vib entropic

Background: During the previous decade a new class of benzamide-based inhibitors 2-trans enoyl-acyl carrier protein reductase (InhA) Mycobacterium tuberculosis (Mt) with unusual binding mode have emerged. Here we report in silico design and evaluation novel benzamide InhA-Mt favorable predicted pharmacokinetic profiles. Methods: By using situ modifications crystal structure N-benzyl-4-((heteroaryl)methyl) (BHMB)-InhA complex (PDB entry 4QXM), 3D models InhA-BHMBx complexes were prepared for...

Background: We have carried out virtual design of coumarinyl-substituted sulfonamides (CSAM) analogs as inhibitors human carbonic anhydrase II (hCA II) endowed with favorable predicted pharmacokinetic profiles and potential therapeutic effects against glaucoma.&#x0D; Methods: modifying in situ the x-ray structure 2-(7-methoxy-2-oxo-2H-chromen-4-yl)-N-(4-sulfamoyl-phenyl)-acetamide (CSAM0)-hCA complex (PDB entry 3ML2), permitted 3D models hCA II-CSAMx complexes preparation for a TS 14 CSAMs...

In recent years, extensive research has been carried out on red blood cells in order to investigate their mechanical properties. The interest these studies possible thanks the technological innovations made field of micro or nano manipulation biological and non-biological particles without physical contact. present project, we have developed a new approach study deformation moving against trapped microbead by applying sinusoidal voltage (DC offset 3.5 Vpp) stage at 0.4 Hz frequencies....