Chikame Dawa Sangma, Dipak Chetia, Malita Sarma Borthakur, Lima Patowary, Dubom Tayeng

Antibiotics kill bacteria by blocking essential metabolic processes which prevent them from reproducing thereby allowing the immune system to fight bacterial infections. However, the emergence and the quick spread of bacterial resistance against clinically approved antibiotics have become alarming. This necessitates the development of novel treatment options and alternative antimicrobial therapies in the fight against bacterial infections. In this study, we aim to virtually design and carry out in silico studies to identify a cephalosporin derivative with inhibitory potential against Haemophilus influenza. Data Warrior software, Discovery studio software, PyRx tool, Swiss ADME web tool, and ProTox-II web tool were used to screen the cephalosporin derivatives. Initially, 17 cephalosporin derivatives were preliminarily screened for their toxicity followed by in silico ADME studies. Among the cephalosporin derivatives, C1, C6, and C12 were found to be the potential drug-like molecules with binding energies of -7.4 kcal/mol, -7.1 kcal/mol, and -7.1 kcal/mol, respectively. In particular, C1 was predicted to have a moderate biological activity with a high bioavailability score. Based on the ADME profile, toxicity, binding energy, drug-likeness, and drug score, we conclude C1 (‘F’ at the 3rd position) as the potential lead molecule to inhibit H. influenza.

Sciences of Phytochemistry

Christy Putri Tari, Octaviana Maria Simbolon, Maria Elvina Tresia Butar-butar

Mixing intravenous preparation, especially in patients' intensive care unit (ICU) at the hospital, requires special attention on their higher medication errors, such as nosocomial infection and incompatibility drugs. The personnel, facilities, infrastructure, and mixing process must be carefully considered when preparing sterile mixtures. This study aims to calculate the percentage of suitability for the mixing process for intravenous preparations based on the Basic Guidelines for Dispensing Sterile Preparations, Guidelines for Injectable and Cytostatic Drugs in 2009, and the Handbook of Injectable Drugs Edition 16th for Intensive Care Unit (ICU) patients at the hospital “X” Samarinda. The research is descriptive research using sheets of observational data collection. The research subjects are mixing facilities, infrastructure, and procedures. We found as many as 215 processes of mixing intravenous preparations in the ICU, showing that nurses carried out 100% of compounding, 100% of the infrastructure did not have a clean room, LAF, and pass box, 53% carried out the mixing process according to procedures, and physical quality tests. Drug preparations follow the Handbook of Injectable Drugs Edition 16th. The preparations produced are clear and free of foreign particles.

Sciences of Pharmacy

Recky Patala, Viani Anggi

Tamoxifen is the most commonly used anti-estrogen adjuvant therapy for estrogen receptor-positive breast cancer. However, it is associated with an increased risk of some serious side effects, such as uterine cancer, stroke, and pulmonary embolism. The flavonoid compounds in the leaves of A. manihot inhibited the growth of 4T1 breast cancer cells at a CTC50 concentration of 185.06 μg/ml. Therefore, this study aims to examine the molecular interactions and pharmacophore modeling based on the interaction of 4-OHT with human ER, followed by the molecular docking of the flavonoid derivatives with human ERα. The molecular docking simulations and 3D structure-based pharmacophore models were used to identify the molecular interactions of flavonoid derivatives in A. manihot on estrogen receptors (ERα) (PDB ID: 3ERT). The results showed that the binding energies of the flavonoid derivatives in isorhamnetin and isoquercitrin were -8.68 kcal/mol and -8.75 kcal/mol, respectively. This compound also interacted with Arg394 and Glu353 important amino acid residues in the ERα-binding pocket. Meanwhile, the pharmacophore fit scores of isorhamnetin and isoquercitrin were 82.36% and 84.91%, respectively. The flavonoid derivatives in A. manihot had pharmacophore fit resulting from the 4-OHT complex with ER, and therefore they had potential as ERα antagonists. Out of the 10 flavonoid derivatives, isorhamnetin and isoquercitrin showed the best docking scores and could be used as candidates for new anti-breast cancer drugs with antagonistic activity against ERα.

Sciences of Pharmacy

Dhunusmita Barman, Nikita Dey, Srijani Sen, Bibhuti B. Kakoti, Catherine Vanlalhriatpuii

Neurological disorders (NDDs) are diseases that affect the central and peripheral nervous systems. Gradual malfunction and destruction of the neurons or the nerve cells characterize them. Every year, NDDs affect millions of people worldwide. Over the years, several neuromodulatory techniques have been introduced to improve the quality of life for those affected by NDDs. NDDs are chronic and incurable conditions, however, bioactive substances derived from medicinal plants have emerged as the greatest choice for their prevention and treatment. Literature evidences several benefits of plant metabolites as alternative medicines for the prevention and treatment of NDDs. Numerous investigations have shown plant metabolites to possess beneficial biological effects because of their qualities, which include but are not limited to anti-inflammatory, antioxidant, and neuroprotective actions. Practices of folk medicine and several studies have also guided many phytopharmacological interventions toward the treatment of NDDs. This review aims to highlight secondary metabolites (alkaloids, flavonoids, steroids, terpenoids) of plants with neuroprotective action that could potentially play an important role in the prevention and management of NDDs.

Sciences of Phytochemistry

Himangshu Sarma, Jon Jyoti Sahariah, Rajlakhsmi Devi, Hemanta Kumar Sharma

In the 21st century, cardiovascular diseases (CVDs) constitute the leading cause of death. It is difficult for potential CVD therapies to be successful since CVDs cannot be effectively or cheaply treated with existing therapy. To formulate and transport therapeutically active molecules to treat a variety of ailments, innovative drug delivery carrier systems have emerged as an efficient method. Their applications have a potential role in routine drug discovery. Heart failure has been studied using a variety of novel treatment approaches, such as cell transplantation, gene transfer or therapy, cytokines, or other small molecules. This review briefly highlights key points in the management of CVDs.

Sciences of Phytochemistry

Lima Patowary, Malita Sarma Borthakur

SARS-CoV-2 is the pathogen responsible for the on-going COVID-19 pandemic. The two proteins namely, spike protein and papain-like protease are mainly responsible for the penetration and transmission of the virus, respectively. The objective of our study was to find the most promising phytoconstituents of Bridelia retusa that can inhibit both the proteins. Molecular docking, protein-ligand interactions, and molecular dynamics (MD) simulation techniques were used in the study. Bepridil and the co-crystal inhibitors of each protein were used as the standards. All the 14 phytoconstituents along with the standard drug and the co-crystal inhibitor of each protein were subjected to molecular docking. Ten compounds showed better binding affinities than the standards against the spike protein and 7 compounds have shown better binding affinities than the standards against papain-like protease protein. From the protein-ligand interactions, a total of 3 out of 10 for the spike protein and 5 out of 7 for the papain-like protease showed better interactions than the standards. An all-atom MD simulations study revealed that (R)4-(1,5-dimethyl-3-oxo-4-hexenyl)-benzoic acid formed the most stable complex with both proteins. The in-silico study provides an evidence for (R)4-(1,5-dimethyl-3-oxo-4-hexenyl)-benzoic acid as a promising inhibitor of the spike and papain-like protease of SARS-CoV-2. Further investigations such as in-vitro/in-vivo studies are recommended to validate the potency of (R)4-(1,5-dimethyl-3-oxo-4-hexenyl)-benzoic acid.

Sciences of Phytochemistry

Igbokwe Mariagoretti Chikodili, Ibe Ifeoma Chioma, Nnorom Miriam Chinwendu, Ejiofor InnocentMary IfedibaluChukwu

The continuous destruction of normal insulin-producing pancreatic beta-cells is a contributing factor in all common forms of diabetes, due to insufficient production of insulin, especially in type 1 diabetes. There are attempts at beta-cells transplantation, but the cost and availability of donors pose a great challenge to the process. Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A (DYRK1A) plays a crucial role in beta-cells destruction. Our research targets to identify plants that can be utilized as a possible alternative approach to beta-cell replacement through a pharmacologically induced regeneration of new beta-cells in-silico. The 3D structure DYRK1A and 6511 phytochemicals were obtained from the Protein Data Bank and the African Natural Products Database respectively. They were duly prepared for molecular docking simulations (MDS). MDS was implemented, after validation of docking protocols, in AutoDock-Vina®, with virtual screening scripts. Phytocompounds with good binding affinities for DYRK1A were selected as frontrunners. The compounds were screened for toxicity, Lipinski’s rule confirmation with Data Warrior software followed by kinase inhibitory bioactivity prediction with the Molinspiration Chemoinformatics web tool. Twelve phytocompounds were found to be predictably highly active in-silico against DYRK1A with good drug-like property based on Lipinski’s rule, non-mutagenic, non-tumorigenic, no reproductive effect, and non-irritant, with high predicted bioactivity. In-silico active phytocompounds against DYRK1A with their plant sources and physicochemical parameters were identified. Further studies will be carried out in-vitro and in-vivo to validate the results of this study using plants containing the identified phytocompounds.

Sciences of Phytochemistry

Amelia Soyata, Kenti Kenti, Meylani Sutoro, Novaliana Devianti Sagita

The co-amorphous solid dispersion system is one of the methods to improve the physicochemical characteristics and stability of a drug. With the appropriate material ratio and preparation method, a co-amorphous solid dispersion system can increase the bioavailability of the drug due to an increase in solubility. In addition, the co-amorphous system will maintain its amorphous shape longer than a single compound. However, using unsuitable materials and methods for co-amorphous fabrication will precipitate them and diminish their bioavailability. As a result, exploring the fundamentals of co-amorphous manufacturing methods is essential. This article discusses the physicochemical properties and solubility of co-amorphous mixtures prepared by solvent evaporation, milling, and quenching methods. Scopus, PubMed, and Google Scholar literature were obtained using the keywords 'co-amorphous preparation', 'co-amorphous method', 'solvent evaporation for co-amorphous preparation', 'milling methods for co-amorphous preparation', and 'quenching method for co-amorphous preparation'. We excluded literature whose application was not in the medical field. Based on the findings, the co-amorphous preparation methods have their respective advantages and disadvantages. Solvent evaporation can only be used on a small scale. Milling techniques are laborious and time-consuming but have a large yield and less chemical destruction, while the quenching method is only intended for thermostable compounds.

Sciences of Pharmacy

Mayang Kusuma Dewi, Reza Pratama, Mia Arifka, Anis Yohana Chaerunisaa

A pharmaceutical industry is highly regulated by a quality policy in its management. The principles of Quality by Design (QbD) must be applied to ensure the development of pragmatic and systematic methods while managing the risks associated with analytical methods. Quality by Design (QbD) is a scientific way to develop easy and robust analytical techniques for critical analysis. Quality by Design (QbD) is a systematic approach to product or method development that starts with predetermined goals and uses a science and risk management approach to achieve product and method understanding. The concept of risk management is deeply integrated into the quality assurance system to ensure pharmaceutical quality and patient safety. In the context of quality control, detecting impurities in raw materials and finished products is a major concern. Analytical Quality by Design (AQbD) aims to achieve quality in measurement. The main objectives are to explain the various steps involved in developing a method using a Quality by Design (QbD) approach for the development of analytical methods and to explain the implementation of Quality by Design (QbD) in the validation of analytical procedures. The advantages of applying Quality by Design (QbD) principles to analytical techniques include finding and minimizing sources of variability that could lead to poor method robustness and ensuring that the method meets the desired performance requirements over the product and method life cycle. The Analytical Quality by Design (AQbD) strategy is increasingly being adopted as it allows an early understanding of the method and guarantees the determination of a wider set of experimental conditions.

Sciences of Pharmacy

Meylani Sutoro, Yuniarti Falya, Restu Harisma Damayanti

Semisolid preparations are widely used to deliver drugs through the skin, cornea, rectal tissue, nasal mucosa, vagina, buccal tissue, urethral membrane, and outer ear lining. They can prevent the first-pass metabolism, reduce side effects, provide immediate local effects, and increase patient compliance. However, an improper manufacturing process will produce a system with bad characteristics, one of which is the mixing process. Several conditions that need to be considered, such as vacuum, temperature, humidity, pressure, stirring speed, stirring time, shear stress, the volume of the mixture, and type of impeller, can affect the consistency, size, and dispersion of particle size, homogeneity, porosity, reactivity, and other characteristics that affect the quality of the semisolid system. Therefore, this article discusses the critical aspects of semisolid mixing, the types, principles, and specifications of several mixer tools and impellers, and how they affect the characteristics of semisolid systems. This review concludes that each type of semisolid preparation requires an impeller and mixer with the specifications and mixing conditions that suit the needs in maintaining the stability and quality of the semisolid system.

Sciences of Pharmacy