From lab to nature: Recent advancements in the journey of gastroprotective agents from medicinal chemistry to phytotherapy.

Peptic ulcer, affecting 10 % of the global population, results from imbalances in gastric juice pH and diminished mucosal defences. Key underlying factors are non-steroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori infection, undermining mucosal resistance. Traditional treatments like proton pump inhibitors (PPIs) and histamine-2 (H2) receptor antagonists exhibit drawbacks such as adverse effects, relapses, and drug interactions. This review extensively explores the ethnomedicinal, synthetic and pharmacological facets of various potential peptic ulcer treatments. Rigorous methodologies involving electronic databases, and chemical structure verification via 'PubChem' and 'SciFinder' enhance the review's credibility. The provided information, spanning medicinal insights to intricate pharmacological mechanisms, establishes a robust groundwork for future research and the development of plant-derived or synthetic molecules for peptic ulcers, offering a promising alternative to conventional therapies.

Molecular modelling approaches can reveal the Molecular interactions established between antimalarial targets of hemozoin pathway and the organic phytochemicals of Artocarpus species.

Ayurveda, the traditional Indian medical system, has potential applications in early malaria treatment. In an in silico docking study, 50 phytochemicals from two plants Artocarpus lakoocha Roxb. (AL) And Artocarpus heterophyllus Lam. (AH), were examined for their interactions with anti-malarial proteins (PDB IDs: 3BWK, 3BPF, 1LF3). The nucleotide analogue Artemisinin, a current malaria treatment, served as a positive control. Result showed that phytochemicals from AL and AH exhibited binding affinities as high as -9.6 kcal/mol, respectively. Additionally, molecular dynamics simulation for Artocarpin: 3BPF demonstrated stable complexes over 100 ns. Notably, Artocarpin and Quercetin displayed higher binding affinities (up to -9.6 as well as -9.5 kcal/mol, respectively) compared to Artemisinin (-7.5 up to kcal/mol), have shown. Pharmacokinetic predictions indicated the compounds were likely non-carcinogenic, water-soluble and biologically safe. In-vitro analysis using ß-Hematin assay supported these findings, suggesting the phytochemicals as Hemozoin pathway inhibitors.

Theoretical and Anti-Klebsiella pneumoniae Evaluations of Substituted 2,7-dimethylimidazo[1,2-a]pyridine-3-carboxamide and Imidazopyridine Hydrazide Derivatives.

A series of multistep synthesis protocols was adopted to synthesize substituted imidazopyridines (IMPs) (SM-IMP-01 to SM-IMP-13, and DA-01-05). All substituted IMPs were then characterized using standard spectroscopic techniques such as 1H-NMR, 13C-NMR, elemental analyses, and mass spectrometry. Our both in vitro qualitative and quantitative results for antibacterial analysis, against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 6051 suggested that all compounds essentially exhibited activity against selected strains of bacteria. Our DFT analyses suggested that the compounds of the SM-IMP-01-SM-IMP-13 series have HOMO/LUMO gaps within 4.43-4.69 eV, whereas the compounds of the DA-01-DA-05 series have smaller values of the HOMO/LUMO gaps, 3.24-4.17 eV. The lowest value of the global hardness and the highest value of the global softness, 2.215 and 0.226 eV, respectively, characterize the compound SM-IMP-02; thus, it is the most reactive compound in the imidazopyridine carboxamide series (except hydrazide series). This compound also depicted lesser MIC values against Klebsiella pneumoniae ATCC 4352 and Bacillus subtilis ATCC 6051 as 4.8 µg/mL, each. In terms of another series, hydrazide DA-05 depicted strong antimicrobial actions (MIC: 4.8 µg/mL against both bacterial strains) and also had the lowest energy gap (3.24 eV), higher softness (0.309 eV), and lesser hardness (1.62 eV). Overall, when we compare qualitative and quantitative antimicrobial results, it is been very clear that compounds with dibromo substitutions on imidazopyridine (IMP) rings would act as better antimicrobial agents than those with -H at the eighth position on the IMP ring. Furthermore, substituents of higher electronegativities would tend to enhance the biological activities of dibromo-IMP compounds. DFT properties were also well comparable to this trend and overall, we can say that the electronic behavior of compounds under investigation has key roles in their bioactivities.

Synthesis, Computational Analysis, Antimicrobial, Antioxidant, Trypan Blue Exclusion Assay, ß-hematin Assay and Anti-inflammatory Studies of some Hydrazones (Part-I).

BACKGROUND: Hydrazone and its azomethine (-NHN=CH-) derivatives are widely reported for their immense pharmacological potential. They have also been reported to possess potent anti-tuberculosis, anti-malarial, anti-inflammatory, and anti-oxidant activities. Considering their pharmacological significance, we herein synthesized a set of 10 hydrazones (1S-10S) using green, biodegradable chitosan and HCl as catalyst. METHODS: All synthesized compounds were characterized using modern spectroscopic techniques, including Nuclear magnetic resonance, 1H-/13C-NMR; Fourier transform infrared spectroscopy (FT-IR); Ultraviolet-visible spectroscopy; Mass spectrometry (m/z), etc. Synthesized compounds were in silico screened using molecular docking, dynamics, pharmacokinetics, theoretical properties, and common pharmacophore analysis. Moreover, we also subjected all compounds to DPPH radical scavenging assay, protein denaturation assay, Trypan Blue assay for cell viability assessments, ß-hematin assay for hemozoin inhibition analysis and standard antimicrobial analysis. RESULTS: Our results suggested that the synthesized compound 2S had high potency against studied microbial strains (minimum MIC = 3.12 µg/mL). Our antioxidant analysis for 1S-10S revealed that our compounds had radical scavenging effects ranging from 25.1-80.3 %. Compounds 2S exhibited % cell viability of 68.92% (at 100 µg concentration of sample), while the same compound retained anti-inflammatory % inhibition at 62.16 %. Compound 2S was obtained as the best docked molecule, with a docking score of -5.32 Kcal/mol with target pdb id: 1d7u protein. Molecular dynamics simulation and normal mode analysis for 100 ns for 1d7u:2S retained good stability. Finally, in silico pharmacokinetics, theoretical properties and pharmacophoric features were assessed. CONCLUSION: In summary, synthesized hydrazone exhibited a good biological profile according to in silico and in vitro studies. However, further in vivo studies are required that may shed more insights on its potencies.

Identification of hydantoin based Decaprenylphosphoryl-ß-D-Ribose Oxidase (DprE1) inhibitors as antimycobacterial agents using computational tools.

Tuberculosis (TB) is one of the emerging infectious diseases in the world. DprE1 (Decaprenylphosphoryl-ß-D-ribose 2'-epimerase), an enzyme accountable for mycobacterial cell wall synthesis was the first drug gable target based on discoveries of inhibitors via HTS (high throughput screening). Since then, many literature reports have been published so far enlightening varieties of chemical scaffolds acting as inhibitors of DprE1. Herein, in our present study, we have developed statistically robust GA-MLR (genetic algorithm multiple linear regression), atom-based as well as field based-3D-QSAR models. Both atom-based as well as field based-3D-QSAR models (internally as well as externally validated) were obtained with robust Training set, R2 > 0.69 and Test set, Q2 > 0.50. We have also developed top ranked 5 point hypothesis AAAHR_1 among 14 CPHs (common pharmacophore hypotheses). We found that our dataset molecule had more docking score (XP mode = - 9.068 kcal/mol) than the standards isoniazid and ethambutol; when docked into binding pockets of enzyme 4P8C with Glide module. We further queried our best docked dataset molecule 151 for ligand based virtual screening using "SwissSimilarity" platform. Among 9 identified hits, we found ZINC12196803 had best binding energies and docking score (docking score = - 9.437 kcal/mol, MMGBSA dgBind = - 70.508 kcal/mol). Finally, our molecular dynamics studies for 1.2-100 ns depicts that these complexes are stable. We have also carried out in-silico ADMET predictions, Cardiac toxicity, 'SwissTargetPredictions' and Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) binding energy calculations for further explorations of dataset as well as hit molecules. Our current studies showed that the hit molecule ZINC12196803 may enlighten the path for future developments of DprE1 inhibitors.

A Systematic Review of updated mechanistic insights towards Alzheimer's disease.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is a degenerative neurological disorder that impairs memory, cognitive abilities, and the ability to do even most everyday activities. This neurodegenerative disease is growing increasingly common as the world's population ages. Here we reviewed some of the key findings that have shown the function of Aß peptide, oxidative stress, free radical damage Triggering Receptors Expressed on Myeloid Cells 2 (TREM2), Nitric Oxide (NO), and gut microbiota in the aetiology of AD. METHODOLOGY: The potentially relevant online medical databases, namely, PubMed, Scopus, Google Scholar, Cochrane Library, and JSTOR were exhaustively researched. In addition, the data reported in the present study were primarily intervened on the basis of the timeline selected from 1 January 2000 to 31 October 2021. The whole framework was designed substantially based on key terms and studies selected by virtue of their relevance to our investigations. RESULTS: Findings suggested that channels of free radicals, such as transition metal accumulation, and genetic factors are mainly accountable for the redox imbalance that assist to understand better the pathogenesis of AD and incorporate new therapeutic approaches. Moreover, TREM2 might elicit a protective function for microglia in AD. NO causes an increase in oxidative stress and mitochondrial damage, compromising cellular integrity and viability. The study also explored that the gut and CNS communicate with one another and that regulating gut commensal flora might be a viable therapeutic for neurodegenerative illnesses like AD. CONCLUSION: There are presently no viable therapies for Alzheimer's disease, but recent breakthroughs in our knowledge of the disease's pathophysiology may aid in the discovery of prospective therapeutic targets.

Antinociceptive Investigations of Niranthin in Complete Freund's Adjuvant-induced Chronic Pain in Mice.

The main objectives of the present work are to determine the clinical effect of niranthin on visceral or somatic inflammatory pain. The study was performed to determine the effects of niranthin on visceral or somatic inflammatory hypersensitivity of adult Swiss albino mice by using complete Freund's adjuvant (CFA) induced pain model. The effect of CFA injection was determined after 24 hours of injection by using an aesthesiometer such as Von Frey filaments to evaluate tactile acetone-evoked cooling and thermal sensitivity. We used a digital Plethysmometer to measure paw edema. Single dose of niranthin intraperitoneal injection (5 & 10 mg/kg) was injected into mice having CFA-induced mechanical hypersensitivity and after 30 minutes of administration, reduced mechanical hypersensitivity was observed. In addition, niranthin also reduced acetone-evoked hypersensitivity within 4 hours. Compared to DMSO, niranthin was most highly active to reduce CFA-induced paw edema. To reduce mechanical hypersensitivity, multiple doses of niranthin (bis in die (b.i.d.)) from 1st - 5th day and b.i.d. day 9th and 10th) were given and remarkable results were observed such as did not cause tolerance in multiple dosing and significantly reduced in CFA induced hypersensitivity. This work reported niranthin having antinociceptive activity and indicated that niranthin is conventionally active in the management of persistent pain.

1,2,5-Thiadiazole Scaffold: A Review on Recent Progress in Biological Activities.

BACKGROUND: Thiadiazoles can be considered as the privileged scaffold having diverse pharmacological potentials such as antihypertensive, anti-HIV, antimicrobials, antileishmanial agents, etc. In particular, 1,2,5-thiadiazoles and their fused analogues are subjects of fast-growing interest due to their higher significance in the fields of biomedicine and material sciences. OBJECTIVE: This study aims to collect detailed medicinal information about aspects of 1,2,5- thiadiazole. METHODS: A systemic search has been carried out using PubMed, Google Scholar, CNKI, etc., for relevant studies having the keyword, '1,2,5-thiadiazole'. RESULTS AND CONCLUSION: In this mini-review, we have covered known procedures of the synthesis and explored in details all known advancements of this scaffold concerning to its biological activities.

Hemozoin (beta-hematin) Formation Inhibitors: Promising Target for the Development of New Antimalarials: Current Update and Future Prospect.

BACKGROUND: Malaria is responsible for social and economic burden in most lowincome malaria-affected countries. Thus, newer antimalarials are needed to tackle morbidities and mortalities associated with the drug-resistant malarial strains. Haemoglobin digestion inside the food vacuole of malarial parasite would lead to producing redox-active and toxic-free heme. The detoxification process adopted by Plasmodium sp. would give rise to hemozoin (Hz) (betahematin) formation. Targeting the pathway of hemozoin formation is considered a validated target for the discovery of newer antimalarials. OBJECTIVE: This study aims to collect detailed information about aspects of hemozoin (Hz) (betahematin) inhibitors. METHODS: A systemic search has been carried out using PubMed, Google Scholar, CNKI, etc., for relevant studies having the keyword, 'hemozoin or beta-hematin' for almost the last 2 decades (2000-2021). RESULTS: This review tries to summarize all the recent advancements made for the developments of synthetic, natural isolated phytoconstituents and plant extracts inhibiting the hemozoin (betahematin) formation. CONCLUSION: Thus they would act as promising antimalarial candidates in the near future.

Effect of dry heating and ionic gum on the physicochemical and release properties of starch from Dioscorea.

To meet the ever increasing industrial demand for excipients with desirable properties, modified starch is regarded as an alternative to it. With this in mind, the present study focuses on the modification of starches of Dioscorea from Jharkhand (India) using dry heat treatment with and without ionic gum. Modified starches were prepared using sodium alginate (1% w/w). Native and modified starches were subjected to heat treatment at 130°C for 2h and 4h. The effect of heating and ionic gum on the properties of Dioscorea starch was investigated. The amylose content, water holding capacity, micromeritic properties, swelling power, solubility and morphology of starches were evaluated. Dry heat treatment of starches without gum showed an increment in water-holding capacity after two-hours heating, but no such increment was found after four-hours heating. Oil binding capacity of starches modified with gum varied from 62% to 78%. Strongest effect of heat treatment occurred on the morphology of starches and thereby modified starches showed distorted surface morphology. Amylose content (21.09-21.89%) found to be decreased with the addition of gum which lead to decrease in paste clarity. Starches heated with gum at high-temperature resulted in restrict swelling and slight increase in solubility. Micromeritic properties of the modified starches showed the good flow properties. Further, the modified starches were investigated for in-vitro release studies and that the thermally modified derivatives can be a good prospect in slow release formulations.

Phytopharmacological Profile of Jasminum grandiflorum Linn. (Oleaceae) / 中国结合医学杂志

Plants are the real basis towards animal life and are also central to people's livelihood. The contributions of the plants in performing varied religious celebrations and in other multiple beneficiaries like medicine, human happiness as well as in treating deadly diseases can never be neglected. In treating diseases, the plants and their constituents are better choice than any other synthetic chemical. The nature has been kind enough to provide the human beings with various types of medicinal plants and in the real sense these form the storehouse of curing almost all the ailments. Consequently, most of the drugs which are being used in preparing formulations have their origin and roots in the plants which form the chief natural source of medicines. Even in modern era, the plant-derived drugs are being extensively used, either in their original or semi-synthetic form. It is because their natural phytoconstituents are highly innocuous posing relatively fewer or no side effects. Based upon their observations, analysis and experience, our ancestors used many plants for medicinal purposes and thus their efforts need to be supported by scientific evidence. Jasminum grandiflorum Linn. is one of such important plants. It has been extensively used by the tribes all over India to treat different diseases which mainly include body pains, toothache, stomach ache, ulcers, and sexual impotency. Chemistry of the plant revealed the presence of mainly secoiridoids, terpenoids, flavonoids and tannins. Not much scientific support was given to the folklore claims for this plant but some of its traditional uses were investigated like spasmolytic, wound healing, antimicrobial, angiotensin converting enzyme inhibitor, antiulcer and antioxidant activities. This article is the review of research works done on the plant Jasminum grandiflorum Linn. to date. As a part of it the local names, morphology, traditional claims, chemistry and pharmacological activities have been discussed.

Physicochemical and release properties of carboxymethylated starches of Dioscorea from Jharkhand.

Increasing demand and considerable attention to the non-conventional sources of starches leads to explore new sources. Starches of Dioscorea (Da1 and Da2) from Jharkhand, North Eastern region of India have been studied for its physicochemical properties. An attempt has been made to study the carboxymethylated derivatives of starches from two varieties of Dioscorea of this region. Different concentration of monochloroacetate was used to study the effect of degree of substitution (DS) on the physicochemical properties of starches. A considerable effect of DS was noticed on the ash content, amylose content, water-holding capacity, swelling and solubility power of carboxymethylated derivatives. Morphological studies showed the increase in the deformation of structure of the starch granule with an increase in the degree of substitution. FTIR confirmed the carboxymethylation reaction. TGA data of carboxymethylated starches revealed the stability to the temperature. Micromeritics of starch powder and granules showed the value which makes these starches to be utilized as an excipient. With the increase in DS, the % release of drug was found to be decreased. This further makes the carboxymethyl derivatives of Dioscorea a good source to be used as an excipient for sustained release formulations.

Preliminary Phytochemical screening and antimicrobial studies on Artocarpus lakoocha Roxb.

The antibacterial activity of Artocarpus lakoocha Roxb. bark was tested against different species of bacteria. The minimum inhibitory concentration (MIC) of the methanolic extract showed that there was no growth in Shigella soneii 2, E.coli MTCC 1568, Bacillus pumilus 8241, Proteus mirabilis AM 198, Bacillus subtelis ATCC 6633, E. Coli Row 7/12 Species at 200-400g/ml. From the result obtained, it was observed that the methanolic extract of. Artocarpus lakoocha at concentration of 200 gl ml and 400 gl ml exhibited a good activity against gram negative bacteria.