Ridla Bakri

Molecular dynamics simulation of complex Histones Deacetylase (HDAC) Class II Homo Sapiens with suberoylanilide hydroxamic acid (SAHA) and its derivatives as inhibitors of cervical cancer

Cervical cancer is second most common cancer in woman worldwide. Cervical cancer caused by human papillomavirus (HPV) oncogene. Inhibition of histone deacetylase (HDAC) activity has been known as a potential strategy for cancer therapy. SAHA is an HDAC inhibitor that has been used in cancer therapy but still has side effects. SAHA modification proposed to minimize side effects. Triazole attachment on the chain of SAHA has been known to enhance the inhibition ability of SAHA and less toxic. In this study, it will be carried out with molecular dynamic simulations of SAHA modifications consisting ligand 1a, 2a and, 2c to interact with six HDAC in hydrated conditions. To all six HDAC Class II, performed docking with SAHA and a modified inhibitor. The docking results were then carried out molecular dynamics simulations to determine the inhibitor affinities in hydrated conditions. The molecular dynamic simulations results show better affinities of ligand 2c with HDAC 4, 6, and 7 than SAHA itself, and good affinity was also shown by ligand 2a and 1c on HDAC 5 and 9. The results of this study can be a reference to obtain better inhibitors.

Utilization of Boron Compounds for the Modification of Suberoyl Anilide Hydroxamic Acid as Inhibitor of Histone Deacetylase Class II Homo sapiens

Histone deacetylase (HDAC) has a critical function in regulating gene expression. The inhibition of HDAC has developed as an interesting anticancer research area that targets biological processes such as cell cycle, apoptosis, and cell differentiation. In this study, an HDAC inhibitor that is available commercially, suberoyl anilide hydroxamic acid (SAHA), has been modified to improve its efficacy and reduce the side effects of the compound. Hydrophobic cap and zinc-binding group of these compounds were substituted with boron-based compounds, whereas the linker region was substituted with p-aminobenzoic acid. The molecular docking analysis resulted in 8 ligands with ΔG binding value more negative than the standards, SAHA and trichostatin A (TSA). That ligands were analyzed based on the nature of QSAR, pharmacological properties, and ADME-Tox. It is conducted to obtain a potent inhibitor of HDAC class II Homo sapiens. The screening process result gave one best ligand, Nova2 (513246-99-6), which was then further studied by molecular dynamics simulations.

The synthesis of 2-(5-(3-methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol using sodium impregnated on activated chicken eggshells catalyst

The novel compound of 2-(5-(3-methoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl)phenol as a pyrazoline derivative has been synthesized by two-steps reaction using sodium impregnated on activated chicken eggshells (Na-ACE) catalyst. Na-ACE was primarily prepared by a simple wet impregnation of NaOH solution on activated chicken eggshells solid support. The Na-ACE catalyst produced was characterized using FTIR spectrophotometer, XRD and SEM then applied in pyrazoline synthesis. First, chalcone was prepared from the reaction of 2-hydroxyacetophenone and 3-methoxybenzaldehyde by base-catalyzed aldol condensation. This product was subsequently reacted with hydrazine hydrate to give corresponding pyrazoline. The structure elucidation of the compound using FTIR, UV-Vis, LC-ESI-MS and 1H-NMR indicated the desired product has been successfully synthesized. Furthermore, the potential antioxidant activities of chalcone and pyrazoline have also been studied in-vitro using DPPH radical scavenging method. The results revealed that pyrazoline has a greater antioxidant activity than chalcone.

Catalytic activity of Na-CaO nanocrystalline for vanillin-based chalcone syntheses

A heterogeneous base catalyst, Na-CaO, was prepared by wet impregnation of NaOH solution on CaO solid support originated from chicken eggshells waste. Material characterization using TGA, FTIR, XRD, SEM, EDAX and BET surface area has confirmed the formation of Na-CaO. The catalyst was applied in chalcone syntheses between acetophenone and vanillin at several reaction conditions, such as various weight of catalyst, temperature, type of solvents and reaction time. The highest yield of product (97%) was obtained from the reaction in ethanol, with 0.3 g of catalyst at 60 °C for 1 hour. This research provides a new route of chalcone syntheses by green environmentally catalyst support of chicken eggshells waste.

In silico modification of Zn2+ binding group of suberoylanilide hydroxamic acid (SAHA) by organoselenium compounds as Homo sapiens class II HDAC inhibitor of cervical cancer

Cervical cancer is the most common cancer in women, and ranks seventh of all cancers worldwide, with 529000 cases in 2008 and more than 85% cases occur in developing countries. One way to treat this cancer is through the inhibition of HDAC enzymes which play a strategic role in the regulation of gene expression. Suberoyl Anilide Hydroxamic Acid (SAHA) or Vorinostat is a drug which commercially available to treat the cancer, but still has some side effects. This research present in silico SAHA modification in Zinc Binding Group (ZBG) by organoselenium compound to get ligands which less side effect. From molecular docking simulation, and interaction analysis, there are five best ligands, namely CC27, HA27, HB28, IB25, and KA7. These five ligands have better binding affinity than the standards, and also have interaction with Zn2+ cofactor of inhibited HDAC enzymes. This research is expected to produce more potent HDAC inhibitor as novel drug for cervical cancer treatment.

Interaction of Purple Sweet Potato Extract with Ascorbic Acid in FeCl3 Solution

Utilization of ascorbic acid as corrosion inhibitor has several weaknesses. These weaknesses are easy to oxidize in solution form and reduction of its antioxidant properties due to heat, light, oxidizing agent, dissolve oxygen, and heavy metals. Purple sweet potato extract is an alternative green corrosion inhibitor with major contains of anthocyanin compound. Anthocyanin will withstand enzymatic reaction and oxidation process of ascorbic acid. Addition of purple sweet potato extract in ascorbic acid will enhance inhibition efficiency of steel compare to the used of ascorbic acid alone. Interaction of purple sweet potato extract with 0.01M ascorbic acid in 0.1M FeCl3 environment was analyzed using FTIR spectroscopy. The result shows that interaction of purple sweet potato extract with ascorbic acid in 0.1M FeCl3 build ability to form iron chelate.

Effects of Purple Sweet Potato Extract Addition in Ascorbic Acid Inhibitor to Corrosion Rate of API 5L Steel in 3.5%NaCl Environment

Using vitamin C or ascorbic acid as corrosion inhibitor has several weakness. In its liquid form ascorbic acid is easily oxidized and its anti oxidant properties unstable due to heat, light, oxidizer, dissolved oxygen and heavy metals. Purple sweet potato (ipomoea batatas L) with its high anthocyanin is one of alternative for green corrosion inhibitor. Extract of purple sweet potato has the ability to hold the enzyme reaction and oxidation proses of ascorbic acid. Purple sweet potato extract mixed with ascorbid acid is used as inhibitor of API 5L steel in 3.5%NaCl. This compound is classifid as mixed type inhibitor. The adding of purple sweet potato extract will assist ascorbic acid to maintance its inhibition efficiency and increases surface layer corrosion resistant of steel. Polarization methods and electrocehmical impedance spectroscopy (EIS) are used to investigate corrosion rate and mechanism of the steel. Appliaction of 4 ml purple sweet potato mixed with 10-4M ascorbic acid inhibitor increases inhibition ability of API 5L steel from 23.5 to 57.52%. Purple sweet potato extract moves polarization curve to lower potential (below 82 mVolt) with tends to be more negative.