Open Access Original Research Article

Molecular Docking and Molecular Dynamic Studies, Synthesis, Characterisation of Thiazolidine-4-One Derivatives

S. Ramachandran, M. Vijey Aanandhi

Journal of Pharmaceutical Research International, Page 1-17
DOI: 10.9734/jpri/2022/v34i27B36000

Background: Antibacterial, antifungal, anticancer, antitubercular, anti-HIV, analgesic, anti-inflammatory, and ulcerogenic activities have all been documented for thiazolidine derivatives. Molecular docking has become a crucial step in the drug discovery process, with the goal of predicting the binding mechanism and affinity of the protein-ligand complex. AutoDock is a popular non-commercial docking tool that successfully docks ligands to their target proteins (accurate and computationally fast). The Discovery Studio Visualizer is a free viewer that may be used to open data produced by other Discovery Studio tools.

Aim: The main aim of this study is:

  • To study the molecular docking and molecular dynamic studies of the different thiazolidine derivatives.
  • To synthesise the compound based on the results produced in the molecular dynamics and molecular studies.
  • To Characterise the synthesised compounds using FTIR, 1H NMR, 13C NMR and Mass Spectral studies.

Procedure: In two phases, a new series of Thiazolidine-4-one derivatives was created. The production of Schiff base is the first step, followed by the condensation of Schiff base with Chloro acetyl chloride and subsequent cyclisation steps. FTIR, 1H-NMR, 13C-NMR, and Mass Spectroscopy were used to characterise the chemical structures of the produced compounds.

1BVR protein that was taken from the protein database website

The structures were drawn using Chem draw Ultra 8.0 and Biovia draw 2018. Using the Smiles Online Translator, it was stored in Mol format and then converted to PDB format. The Cygwin toolings were used to log all of the files.

Conclusion: The conformation was computed using a ranking system. This indicates whether the molecule has strong ligand binding energy, hydrogen bonding, and hydrophobic interaction with the receptor. According to the findings, thiazolidine-4-one derivatives have antitubercular efficacy when used in conjunction with the Enoyl-acyl carrier protein (enoyl-ACP) reductase enzyme.

For the docking analysis it indicates if the compound has strong ligand binding energy, hydrogen bonding, and hydrophobic binding with the receptor shows good activity. Using Auto dock 4.2 it was found out that among the above 20 compounds (including the control compound), C2, C5, C6, C8, C11. C13, C15 and C17 directly bind with the functional domain (Casein kinase II phosphorylation site) of the amino acid (252 to 255). The above compounds bind at the 252nd position of the Chain C, where Alanine is present (The target protein, 1BVR () contains ABCDEF chains).

Open Access Original Research Article

Induction of Bax and Activation of Caspases Hydro Ethanoic Leaf Extract of Citrullus colocynthis(L)- Mediated Apoptosis in Human Liver Cancer Cells Hep G2

K. Swetha, A. Jothi Priya, Selvaraj Jayaraman, R. Gayatri Devi

Journal of Pharmaceutical Research International, Page 18-24
DOI: 10.9734/jpri/2022/v34i27B36001

Introduction: Citrullus colocynthis is a desert plant of the cucurbitaceae family. C. colocynthis grows in many countries with semi dry lands and that seeds are rich in oil which can encourage their sustainable agriculture to produce an economic biodiesel with a competitive price. Apoptosis, also termed as programmed cell death this is a key regulator of tissue homeostasis.

Aim of the Study: To study the induction of bax and activation of caspases hydro ethanolic leaf extract of Citrullus colocynthis (L)- mediated apoptosis in human liver cancer cells Hep G2.

Materials and Methods: In the present study, a human liver cancer cell line was procured from the National Centre for Cell science (NCCS), Pune, India. The cytotoxic potential of plant extract was analysed by MTG assay. mRNA expression of BaxmRNA and caspase-mRNA were analysed by Real-Time PCR using gene specific primers and a comparative CT method was used to analyse expression of genes. The data were analysed statistically using Graph pad prism software         Version 5.

Results:  MTT analysis showed that Citrullus colocynthis a significant increase in proliferation of human liver cancer cells (P<0.05) compared to untreated cells. However, 400 and 500 /g of the extract showed maximum effect in controlling cell growth. Results of the <mRNA expression analysis showed that Citrullus colocynthis reduced the expression of BaxmRNA/ caspase-mRNA in human liver cancer cells at 400 and 500 /g (P<0.05).

Discussion: The anticancer effect of Citrullus colocynthis has been via a variety of pathways which includes apoptotic pathway, anti-inflammatory traits, and antioxidant pathway, etc [1]. Effect of HEAM on the mRNA level of tumor related genes (p53, Bcl-2), inflammatory (IL-1β, IL-6 and c-jun) and anti-inflammatory (IL-4) cytokines. Representative photographs of ethidium-bromide-stained 2% agarose gels for each gene after 7 months of treatment.

Conclusion: The hydroethanolic leaf extract obtained from the Citrullus colocynthis exhibited anti-proliferative effect on human liver cancer cells HepG2 cell line by affecting the expression of the Bax mRNA and Bax mRNA and hindering the cell viability. Hence, it can be a great scope for using the extract into medicinal properties with further studies to improve herbal medicine for cancer over expensive drugs.

Open Access Original Research Article

Assess the Mean Change in Outcomes of Sildenafil in the Treatment of Lower Urinary Tract Symptoms and Erectile Dysfunction Due to Benign Prostatic Hyperplasia

Arif Ali, Shahid Hussain, Bilal Suria, Safiullah Sohu, . Murtaza, Suhail Dilawar

Journal of Pharmaceutical Research International, Page 25-32
DOI: 10.9734/jpri/2022/v34i27B36002

Objective: To assess the mean change in outcomes of sildenafil in the treatment of lower urinary tract symptoms and erectile dysfunction due to benign prostatic hyperplasia.

Study Design: This is a quasi experimental study.

Setting: The study was carried out at OPD of Department of Urology, Jinnah Postgraduate Medical Centre, Karachi, from January 26, 2018 to July 26, 2018.

Materials and Methods: 50 patients fulfilling selection criteria were included in the study through OPD of Department of Urology, Jinnah Postgraduate Medical Centre, Karachi Informed consents were obtained. Demographics (name, age and contact) were also be obtained. All patients were subjected to detailed history and clinical examination for BPH and ED according to the IPSS and IIEF. Mean change in urine flow rate assessed through uroflowmetry and Mean change in post-void residual (PVR) urine was assessed through an ultrasound on the same day and on follow-up after 10th weeks in OPD before and after the tablet sildenafil 50 mg OD at night to every patient.

Results: Mean age of patients was 58.42±9.76 (45-80) years. pre and post treatment International prostate symptom score (IPSS) score mean 17.78±2.91 and 12.94±2.79 (p-value=0.0001) respectively, erectile function score (IIEF) score mean 17.64±2.69 and 21.86±4.47 (p-value=0.0001) respectively, Urinary flow rate (UFR) pre and post treatment mean 8.32±1.62 and 12.46±1.83 (p-value=0.0001) respectively, Post-void residual (PVR) urine pre and post treatment mean 62.64±6.29 and 54.72±5.04 (p-value=0.0001) respectively.

Conclusion: Improvement of erectile dysfunction and reduction of urinary tract symptoms in men with sildenafil was associated with improved quality of life and satisfaction with treatment. Daily doses of sildenafil can improve lower urinary tract symptoms.

Open Access Original Research Article

Design, Synthesis of Mannich Bases Derivatives of Thiosemicarbazide and their Evaluation for Anticancer Activity using Potato Disk Bioassay Method

Geetanjali Sandip Patil, Sachin Ashok Pishawikar

Journal of Pharmaceutical Research International, Page 53-62
DOI: 10.9734/jpri/2022/v34i27B36007

Mannich bases and thiosemicarbazide individually are known to show verity of pharmacological activities such as anti-inflammatory, anticancer, antifilarial, antibacterial, antifungal, anticonvulsant, anthelmintic, antitubercular, analgesic, anti-HIV, antimalarial, antipsychotic, antiviral and so forth.  As novel attempt in present work in first step synthesis of verity of mannich bases is done using structurally different types of aldehyde, ketones and amines. The condensation of synthesized mannich bases is done with thiosemicarbazide to form a novel class of compounds called mannich bases of thiosemicarbazide. Use of bioassay is one of the ways of carrying out preliminary investigation of activity. A. tumefaciens induced potato disc tumor assay has been used to investigate anticancer activity of synthesized compounds. The compounds B2, B4, B25, B26, B28, B29 and B30 have shown same or better inhibitory activity compared to Gemcitabine used as standard.

Open Access Original Research Article

Investigation of the Effect of Methylprednisolone on Neck Pain

Khalil Komlakh, Masoud Hatefi

Journal of Pharmaceutical Research International, Page 93-97
DOI: 10.9734/jpri/2022/v34i27B36009

Background: Chronic Neck pain (NP) is one of the most common problems. Therefore, the present study was conducted with an aim Investigation of the effect of prednisolone on NP.

Methods: In this clinical trial, with 46 patients for the experimental group and 43 patients were analyzed for the control group. The method of selecting individuals in both groups was sequentially, thus all eligible individuals were selected to complete the sample size required. The statistical population of patients with NP was referred to clinics, hospitals and specialist doctors. Data were collected using the VAS pain scale, which was in the range of zero-10, before and after the intervention and analyzed using SPSS16 software.

Result: The results showed that the M (SD) pain score before the intervention in the control group was 7.32±0.47 and in the experimental group was 7.20±0.41(P=0.21, F=6.27). After drug treatment with methylprednisolone in 3 days after M (SD) intervention the pain of patients in the experimental group decreased to 5.50±0.88, in 6 days to 3.60±0.53 and in 9 days to 3.26±0.68(P=0.000).

Conclusions:
Due to the positive effect of methylprednisolone on reducing pain in patients with NP, the use of this drug is recommended to reduce pain in these patients.

Open Access Review Article

Recent Advancements in Gibberellic Acid Formulation Techniques and Economics of Use in Agriculture

Avinash Tupe, Atul Baravkar, Ganesh Devkate

Journal of Pharmaceutical Research International, Page 33-41
DOI: 10.9734/jpri/2022/v34i27B36005

Gibberellins comprises of a broader family of plant advancement hormones found during the 1930s, which are synthesized by implies of the terpenes course from the geranylgeranyl diphosphate and incorporate a crucial structure formed by an ent-gibberellane tetracyclic skeleton. Among them Gibberellic acid (GA3 ), which acts as a characteristic plant development controller, especially for stem extending, seed germination, and extended common item degree. It can be gotten from plants, organisms, and microbes. There are as well a couple of reports roughly microalgae GA3 makers. Life forms, especially Gibberella fujikuroi, are favored for GA3 generation through submerged maturing or solid-state development. Various factors may impact its generation, a few of which are related to the control and scale-up of maturing parameters. Particular GA3 items are open on the advertise. They can be found in liquid, powder, tablet, beads and granule dosage forms containing because it were GA3 or a mix of other normal dynamic gibberellins, which can be employed in agriculture, horticulture & floriculture crops.

Open Access Review Article

Updates in Causes, Risk Factors, Diagnosis and Management of Lichen Planus

Samiah Abdulrahman Abanomy, Abdulaziz Saqer A. Alanazi, Jehad Ahmed Alabdulminaim, Laila Shuqayr Alrashidi, Maram Nasser Alawlah

Journal of Pharmaceutical Research International, Page 42-52
DOI: 10.9734/jpri/2022/v34i27B36006

Bhutani et al. originally described a pigmented variety of lichen planus (LP) from India in 1974, and created the label LP pigmentosus (LPP) to better describe it. LPP is one of several variations of the LP gene. This skin lesion has also been reported in the Middle East, Latin America, Korea, and Japan, and is more common in those with darker skin. The most common differential diagnosis for LPP is erythema dyschromicum perstans (EDP). Fixed drug eruption, macular amyloidosis, urticaria pigmentosa, tar melanosis, frictional melanosis, berloque dermatitis, pigmented beautifying dermatitis (Reihl's melanosis), and pigmented beautifying dermatitis (Reihl's melanosis) are some of the other differences. Cutaneous LP usually clears up on its own after 1 to 2 years, thus care focuses on lowering pruritus and speeding up the healing process. First-line management for limited LP is superpotent interesting steroids (clobetasol 0.05%) twice daily for 2 to 4 weeks.

This study aims to:

1- Recognize the causes and risk factors for lichen planus

2- Correct diagnosis of lichen planus

3- Provide effective treatment for lichen planus

Open Access Review Article

Nanotherapeutic Drug Synthesized by Way of a Microbial Pathway Targeting Staphylococcus aureus

Ziaullah M. Sain

Journal of Pharmaceutical Research International, Page 63-92
DOI: 10.9734/jpri/2022/v34i27B36008

Staphylococcus aureus (S. aureus) is one of the most common human pathogens causing various infectious diseases. Further, its ability to form biofilm and the emergence of antibiotic resistance strains has made it difficult to treat the infection. A nanoparticle-based therapeutic approach is an emerging area to treat S. aureus infection. Among the different methods to synthesize nanoparticles (NPs), the use of microorganisms to fabricate metal nanoparticles with the antibacterial property against S. aureus has been investigated by several studies. The microbial approach is cost-effective, eco-friendly, and devoid of toxic byproducts produced in other methods of nanoparticles formation. The review details the use of bacteria, fungi, yeast, algae, and lichens for producing nanoparticles of various metals, such as silver, gold, zinc, copper, iron, cerium, etc., of varying sizes and shapes and their effective use against S. aureus. The present review focuses on the reports of microbial-fabricated nanoparticles as therapeutic agents for treating S. aureus infection.

Open Access Review Article

A Review on the Therapeutic Management of COVID-19 Associated with Thrombotic Events and Coagulopathies

R. Vigneswaran, S. R. Senthil Kumar, T. Venkatachalam, P. Kalaiselvi, K. Sattanathan, R. Rajaguru, N. Srinivasan

Journal of Pharmaceutical Research International, Page 98-105
DOI: 10.9734/jpri/2022/v34i27B36010

Severe acute respiratory syndrome coronavirus two (SARS-CoV-2) is answerable for the coronavirus illness in 2019 (COVID-19) that chop-chop evolved from a virus in metropolis, Varied coagulopathies are rumored in association with COVID-19, together with disseminated intavasular action (DIC) sepsis-induced coagulopathy (SIC), native microthrombi, blood vessel occulation (VTE), blood vessels thrombotic complications and thrombo inflammation. There’s a overplus of publications and conflicting information on hematologic and astringent derangements in COVID-19 with some information suggesting the link to illness progress, severity and/or mortality. There is also growing evidence of potentially usefull clinical biomarkers to predict COVID-19 progression and illness outcomes of these, a link between blood disease and COVID-19 severity or mortality was instructed. During this opinion report, we have a tendency to examine the revealed proof of hematological and astringent laboratory derangements in COVID-19 and also the reticular SARS-CoV-2 evoked inflammation, with a focused discussion on blood platelet count alterations.

Open Access Review Article

Transferosomes: Vesicular Carrier for both Hydrophilic and Lipophilic Drugs

R. Santosh Kumar, Maharnab Pradhan

Journal of Pharmaceutical Research International, Page 106-120
DOI: 10.9734/jpri/2022/v34i27B36013

The vesicular system has accessed significant importance towards a sustained drug delivery system in recent years. This article was designed to review the future of vesicular systems known as transferosomes. The vesicles are softer and highly deformable than liposomes. The word Transferosomes is derived from Latin and Greek words called “Transferre” and “soma,” respectively, where Transferre means “carry across” and Soma means “a body.” Transferosomes vesicles are carrying bodies for targeted transdermal drug delivery systems. It consists of phospholipid and an edge activator. In transferosome, phospholipids vesicles act as transdermal drug carriers. It generates an osmotic gradient at the stratum corneum and helps the transferosomes penetrate through the stratum corneum by the transcellular route. Transferosomes have a wide range of solubility, have a remarkable ability to penetrate through the skin, are compatible and biodegradable, and are highly expensive. But they are easily prone to chemical degradation and are highly expensive. The transfersomes were formulated by handshaking, vortex, and freeze-thaw techniques. Transferosomes have various Evaluation parameters such as Vesicle size distribution, the morphology of vesicle, Number of vesicles per cubic mm. Transferosomes have various applications like they can be applied in controlled release and sustained release formulation, transportation of lower and higher molecular weight drug molecules, target drug delivery system, and transdermal immunization. Transferosomes have been ultra-deformable vesicles capable of subjecting a futuristic solution to all vesicular delivery and conventional delivery complications. It can carry any drug’s molecular weight through the skin; due to its ultra-deformable characteristics feature, therefore, they are widely used to take protein and peptides. After doing all the evaluation studies, we can say that Transferosomes are the promising candidate for the vesicular system and can replace other novel vesicular systems. Thus it holds a bright future in novel drug delivery systems.