IPS Journal of Molecular Docking Simulations

Bioactive compounds found in Cucumis sativus demonstrate optimal binding affinity to PTP1B.

Sat, 14 Oct 2023 00:00:00 -0600

Diabetes mellitus is a group of cardiometabolic disorders defined by elevated blood sugar levels. The majority of people affected by this disease reside in rural areas of low- and middle-income countries. The PTP1B inhibitory enzyme is involved in the control of leptin and insulin signaling. The Cucumis sativus plant, which includes several phytochemical constituents, has been shown to have antidiabetic properties. This study examines the in silico inhibitory potential of bioactive compounds obtained from Cucumis sativus against a potentially diabetogenic enzyme, PTP1B. (Trodusquesmine). The analysis resulted in scores for the first five compounds (isoorientin, chlorogenic acid, isovitexin, caffeic acid, and ferullic acid) ranging from -8.60 to -6.44 kcal/mol. The MM-GBSA of each ligand is expressed as follows: -56.46, -51.13, -51.63, -53.06 and -52.65 ΔGbind. Researchers are looking for plants that can be used as stable treatments with few side effects, although many drugs are already used to treat diabetes. As a result, the molecular bond, generalized molecular mechanics surface area (MM-GBSA) and properties of the lead compound ADMETox were determined.

In silico and In vivo Studies of Calotropis procera leaf and root extracts on Mitochondrial-Related parameters in Wistar Rats

Sun, 03 Sep 2023 00:00:00 -0600

Drugs targeting Mitochondrial Membrane Permeability Transition (MMPT) pore opening are of great interest for conditions arising from apoptosis dysregulation. This study investigate MMPT pore inducing effect of Calotropis procera leaves and root extracts on mitochondrial-related parameters in the liver of healthy male Wistar rats. Extraction was done by standard methods, using Ethylacetate and Butanol solvent. Fifty–two rats weighing between 130 g - 150 g were divided into thirteen groups (n=4). Group 1 received distilled water, other groups were administered ethylacetate leaf extract (ELE), butanol leaf extract (BLE), ethylacetate root extract (ERE) and butanol root extracts (BRE). Liver Mitochondrial pore opening, mitochondrial ATPase activity and lipid peroxidation were assessed spectrophotometrically, while the interaction between human Cyclophilin D (a pore activating protein with PDB ID: 2BIT) and identified phytochemicals of Calotropis procera leaves and roots extracts were studied In-silico. Varying concentrations of the extracts induced MMPT pore opening by 6.6, 7.4 and 5.9 folds for BLE and 10.2, 7.3 and 6.4 folds for ELE at 40, 50 and 60 mg/100g bw respectively when compared with control group. Root extracts showed significant MMPT pore opening with a fold increase of 12.2, 10.1 and 20.4 for BRE and 11.37, 11.84, for ERE at at 40 , 50 and 60 mg/100g bw respectively. BLE, BRE, ELE and ERE showed increase in ATPase activities with respect to the control group. Malondialdehyde (MDA) levels as an indication of lipid peroxidation increased significantly when compared with control. Molecular docking and simulation showed the existence of stable interactions between human Cyclophilin D with phytochemicals of Calotropis procera with 2‶-Oxovoruscharin having highest binding affinity of -7.9 kcal/mol. C. procera has potential for therapeutic use for the treatment of disorders related to derangement of apoptosis.

Application of In-silico Methodologies in Exploring the Antagonistic Potential of Trigonella foenum-graecum on Cyclooxygenase-2 (Cox-2) in Cancer Treatment

Fri, 15 Sep 2023 00:00:00 -0600

Cancer is a disease in which abnormal cells divide uncontrollably and destroy body tissue. This research is dispensed utilizing in-silico drug design. Cyclooxygenase-2 (Cox-2) has been used as a target protein of the molecular docking study and fenugreek phytoconstituents obtained from PubChem were docked against Cox-2’s pocket (PDB ID: 5IKV). We used Maestro 12.8 and the Schrödinger Suite to conduct computer-based drug testing. To document compounds with the best inhibitory ability to act as cyclooxygenase antagonists in the treatment of cancer. Sixty (60) compounds described with fenugreek were docked to the active site of Cox-2 (5IKV). The results demonstrated that tricin to 2,5-dimethyl pyrazine, which are the best molecules docked at the active site of Cox-2, had -11.007 to -4.58 kcal/mol and an MM-GBSA score ranging from -31.06 to -24.52 respectively, which suggests the free binding energy posed competitive binding energy when compared to the co-crystallized ligand, 2-[[3-(Trifluoromethyl) Phenyl] Amino] Benzoic Acid. Numerous drugs have been made available, but due to their common side effects, researchers are now searching for novel herbal plants that can be utilized as long-term treatments with minimal adverse effects. Thus, utilizing computational studies such as molecular docking, MM-GBSA, pharmacophore modeling, and the lead compounds’ ADMETox characteristics were computed.