An Insight into the Repurposing of Phytoconstituents obtained from Delhi's Aravalli Biodiversity Park as Antifungal Agents.

The global prevalence of fungal infections is alarming in both the pre- and post- COVID period. Due to a limited number of antifungal drugs, there are hurdles in treatment strategies for fungal infections due to toxic potential, drug interactions, and the development of fungal resistance. All the antifungal targets (existing and newer) and pipeline molecules showing promise against these targets are reviewed. The objective was to predict or repurpose phyto-based antifungal compounds based on a dual target inhibition approach (Sterol-14-α- demethylase and HSP-90) using a case study. In pursuit of repurposing the phytochemicals as antifungal agents, a team of researchers visited Aravalli Biodiversity Park (ABP), Delhi, India, to collect information on available medicinal plants. From 45 plants, a total of 1149 ligands were collected, and virtual screening was performed using Schrodinger Suite 2016 software to get 83 hits against both the target proteins: Sterol-14-α-demethylase and HSP-90. After analysis of docking results, ligands were selected based on their interaction against both the target proteins and comparison with respective standard ligands (fluconazole and ganetespib). We have selected Isocarthamidin, Quercetin and Boeravinone B based on their docking score and binding interaction against the HSP-90 (Docking Score -9.65, -9.22 and -9.21, respectively) and 14-α-demethylase (Docking Score -9.19, -10.76 and -9.74 respectively). The docking protocol was validated and MM/GBSA studies depicted better stability of selected three ligands (Isocarthamidin, Quercetin, Boeravinone B) complex as compared to standard complex. Further, MD simulation studies were performed using the Desmond (67) software package version 2018-4. All the findings are presented as a case study for the prediction of dual targets for the repurposing of certain phytochemicals as antifungal agents.

Blending Ethnomedicine with Modern Technology-From Conventional to Tailored Products: Modulating Biopharmaceutical Properties of Berberis Extract by Solid Lipid Nanoparticles for Wound Healing.

Drug-delivery systems employing phytopharmaceuticals based on the leads in traditional knowledge offers not only an alternative but quicker and more economic strategy for drug development. Nanophytopharmaceuticals promise remarkable opportunities with the ability to overcome challenges associated with herbal medicines, such as low solubility and bioavailability, poor target specificity, and shelf life. Berberis extracts documented as Ropana (wound healer) in Sushruta Samhita are a popular traditional remedy that is amiss in the modern system of medicine as it exhibits very poor biopharmaceutical properties. Poor solubility and bioavailability necessitate the administration of high doses to achieve the desired therapeutic effects. Exploiting the diversified type of compounds with pleiotropic properties present in Berberis, the biopharmaceutical properties were engineered using an optimized freeze-dried extract and developed solid lipid nanoparticles (SLNs) as an effective drug-delivery system. An industrially viable and environment-friendly hot high-pressure homogenization technique led to a stable formulation with an average particle size of 178.4 nm, as well as a 7-fold increase in loading and a significant entrapment of 91 ± 1.25%. The pharmacodynamic studies of developed nanosystems in excision-wound models showed faster and complete healing of wounds with no scars.

Site dependence of the magnetocaloric effect in Mn5-x Fe x Si3.

The nuclear and magnetic structures of Mn3Fe2Si3 are investigated in the temperature range from 20 to 300 K. The magnetic properties of Mn3Fe2Si3 were measured on a single crystal. The compound undergoes a paramagnetic to antiferromagnetic transition at T N2 ≃ 120 K and an antiferromagnetic to antiferromagnetic transition at T N1 ≃ 69 K. A similar sequence of magnetic phase transitions is found for the parent compound Mn5Si3 upon temperature variation, but the field-driven transition observed in Mn5Si3 is not found in Mn3Fe2Si3, resulting in a strongly reduced magnetocaloric effect. Structurally, the hexagonal symmetry found for both compounds under ambient conditions is preserved in Mn3Fe2Si3 through both magnetic transitions, indicating that the crystal structure is only weakly affected by the magnetic phase transition, in contrast to Mn5Si3 where both transitions distort the nuclear structure. Both compounds feature a collinear high-temperature magnetic phase AF2 and transfer into a non-collinear phase AF1 at low temperature. While one of the distinct crystallographic sites remains disordered in the AF2 phase in the parent compound, the magnetic structure in the AF2 phase involves all magnetic atoms in Mn3Fe2Si3. These observations imply that the distinct sites occupied by the magnetic atoms play an important role in the magnetocaloric behaviour of the family.

Bioactivity and In Silico Studies of Isoquinoline and Related Alkaloids as Promising Antiviral Agents: An Insight.

Viruses are widely recognized as the primary cause of infectious diseases around the world. The ongoing global pandemic due to the emergence of SARS-CoV-2 further added fuel to the fire. The development of therapeutics becomes very difficult as viruses can mutate their genome to become more complex and resistant. Medicinal plants and phytocompounds could be alternative options. Isoquinoline and their related alkaloids are naturally occurring compounds that interfere with multiple pathways including nuclear factor-κB, mitogen-activated protein kinase/extracellular-signal-regulated kinase, and inhibition of Ca2+-mediated fusion. These pathways play a crucial role in viral replication. Thus, the major goal of this study is to comprehend the function of various isoquinoline and related alkaloids in viral infections by examining their potential mechanisms of action, structure-activity relationships (SAR), in silico (particularly for SARS-CoV-2), in vitro and in vivo studies. The current advancements in isoquinoline and related alkaloids as discussed in the present review could facilitate an in-depth understanding of their role in the drug discovery process.

Structural-Distortion-Driven Magnetic Transformation from Ferro- to Ferrimagnetic Iron Chains in B6 -based Nb6 FeIr6 B8.

We report on a structural distortion of kinetically stable B6 -based ferromagnetic Nb6 FeIr6 B8 that induces an unprecedented transformation of a ferromagnetic Fe chain into two ferrimagnetic Fe chains through superstructure formation. Density functional theory calculations showed that the ferromagnetic Fe-Fe intrachain interactions found in the undistorted structure become ferrimagnetic in the distorted superstructure, mainly because the two independent iron atoms building each chain interact antiferromagnetically and carry different magnetic moments. High-temperature SQUID magnetometry confirmed ferrimagnetic ordering at 525 K with a high and negative Weiss constant of -972 K indicating the presence of strong antiferromagnetic interactions, as predicted. This finding paves the way for the development of low-dimensional magnetic intermetallic systems based on Heisenberg ferrimagnetic chains, which have previously been studied only in molecular-based compounds.

Pressure induced effects on the chemical and magnetic structure of spinel MnV2O4.

The influence of external pressure (P ⩽ 5 GPa) on both the structural and magnetic ordering in MnV2O4 has been investigated using neutron diffraction technique. The volume and the V-V distance decrease with pressure while the c/a ratio increases, suggesting a lowering of the distortion with pressure. Under ambient conditions this compound exhibits a structural transition (T S) from tetragonal to cubic at ~53 K and a magnetic transition (T N ) at ~56 K. It is found that with an increase in pressure to 5 GPa, T N increases (from 56 K to 80 K), dT N /dP > 0, while T S decreases (from 53 K to 37 K). The non collinear magnetic structure in the tetragonal phase at 5 GPa and 10 K remains the same as at ambient pressure. However, the Mn and V sublattice, now exhibits distinct transition temperatures, [Formula: see text] ~ 80 K, and [Formula: see text] ~ 60 K. The transition to the cubic phase at T S is accompanied by a collinear alignment of the Mn and V spins and a reduction in the Mn moment. The region in which the structure remains in the cubic phase with collinear magnetic structure increases with pressure from ~3 K at ambient pressure to ~43 K at 5 GPa pressure.

Current Perspective in the International Trade of Medicinal Plants Material: An Update.

BACKGROUND: The recent years have seen an increased interest in medicinal plants together with the therapeutic use of phytochemicals. Medicinal plants are utilized by the industry for the production of extracts, phytopharmaceuticals, nutraceuticals and cosmeceuticals and their use is expected to grow faster than the conventional drugs. The enormous demand of medicinal plant material has resulted in huge trade both at domestic and international levels. METHODS: The trade data of medicinal plant material with commodity code HS 1211 (SITC.4, code 292.4) and their derived/related products which are traded under different commodity codes has been acquired from COMTRADE, Trade Map, country reports, technical documents etc for the period 2001 to 2014. The data was analyzed using statistical tools to draw conclusions. RESULTS: The significant features of the global trade; the leading source, consumer, import and export countries; and the striking trends are presented. The trade of the ten key countries and the selected important items is also discussed in detail. The conservative figure of trade of medicinal plants materials and their derived/related products including extracts, essential oils, phytopharmaceuticals, gums, spices used in medicine, tannins for pharmaceutical use, ingredients for cosmetics etc. as calculated from the global export data for the year 2014 is estimated at USD 33 billion. The average global export in medicinal plants under HS 1211 for the fourteen year period was USD 1.92 billion for 601,357 tons per annum and for the year 2014 it stood at 702,813 tons valued at USD 3.60 billion. CONCLUSION: For the studied period, an annual average growth rate (AAGR) of 2.4% in volumes and 9.2% in values of export was observed. Nearly 30% of the global trade is made up by top two countries of the import and export. China and India from Asia; Egypt and Morocco from Africa; Poland, Bulgaria and Albania from Europe; Chile and Peru from South America are important supply sources. The USA, Japan and Europe are the major consumers of the world.

Amelioration of testosterone induced benign prostatic hyperplasia by Prunus species.

ETHNOPHARMACOLOGICAL RELEVANCE: Benign prostatic hyperplasia (BPH) is a common urological disorder of men. The ethnomedicinal use of an African plant Prunus africana (Hook.f.) Kalkman (Pygeum) in treating men's problems made it a popular remedy all over the globe for the treatment of BPH and related disorders. However, rampant collections made from the wild in Africa have pushed the plant to Appendix II of CITES demanding conservation of the species. AIM OF THE STUDY: In the present study, the aim was to unearth the protective effect of bark of different species of Prunus against BPH. The five selected Indian plants of family Rosaceae viz. Prunus amygdalus Stokes, Prunus armeniaca L., Prunus cerasoides Buch.-Ham. ex D. Don, Prunus domestica L. and Prunus persica (L.) Batsch were evaluated against P. africana (Hook.f.) Kalkman for a suitable comparison of efficacy as antiBPH agents. MATERIALS AND METHODS: The antiBPH activity was evaluated in testosterone (2mg/kg/day, s.c, 21 days) induced BPH in Wistar rats. The parameters studied were body weights; histopathological examination, immunohistochemistry (PCNA) and biochemical estimations of the prostate; supported by prostatic index, testicular index, creatinine, testosterone levels; antioxidant and anti-inflammatory evaluation. The study also included chemical profiling using three markers (ß-sitosterol, docosyl ferulate and ursolic acid) and estimation of ß-sitosterol content through GC. RESULTS: The Prunus species showed the presence of all the three markers in their TLC fingerprint profile and maximum amount of ß-sitosterol by GC was observed in P. domestica. Interestingly, all the species exhibited significant amelioration in testosterone induced parameters with P. domestica showing the most encouraging effect as indicated from histopathological examination, immunohistochemistry and biochemical studies. The Prunus species further showed remarkable anti-inflammatory and antioxidant activity signifying their role in interfering with various possible factors involved in BPH. CONCLUSIONS: These findings are suggestive of a meaningful inhibitory effect of testosterone induced BPH by the bark of different species of Prunus in the order of P. domestica, P. persica, P. amygdalus, P. cerasoides and P. armeniaca with an efficacy of P. domestica comparable to P. africana and can be used as the potential backup of Pygeum for the management of BPH.

Novel dual inhibitors of nuclear factor-kappa B (NF-κB) and cyclooxygenase- 2 (COX-2): synthesis, in vitro anticancer activity and stability studies of lantadene-non steroidal anti-inflammatory drug (NSAID) conjugates.

The activation of transcription factors nuclear factor-kappa B (NF-κ B) and cyclooxygenase-2 (COX-2) is critical in cancer; they act synergistically in promoting tumor growth, survival, and resistance to chemotherapy. Thus, combined targeting of NF-κ B and COX-2 present an opportunity for synergistic anticancer efficacy. The ester prodrugs of pentacyclic triterpenoids reduced lantadene A (3), B (4), and its congener 22ß-hydroxyoleanonic acid (5) with various non steroidal anti-inflammatory drugs (NSAIDs) present a novel approach. The ester prodrugs of 3 and 4 with diclofenac showed promising dual inhibition of NF-κ B and COX-2. The lead prodrugs 14 and 15 exhibited inhibition of inhibitor of nuclear factor-kappa B kinaseß (IKKß) in the single-digit micromolar range and at the same time, prodrugs 14 and 15 showed marked cytotoxicity against A549 lung cancer cell line with IC(50s) 0.15 and 0.42 µM, respectively. The prodrugs 14 and 15 exhibited stability in the acidic pH and were hydrolyzed readily in the human blood plasma to release the active parent moieties. Thus, we have synthesized novel hybrid compounds to target both NF-κ B and COX-2 via a prodrug approach, leading to promising anticancer candidates.

Synthesis and evaluation of antioxidant-s-(+)-Ibuprofen hybrids as gastro sparing NSAIDs.

Ibuprofen is one of the most popular NSAIDs for the last three decades but also known for its gastrointestinal side effects similar to other NSAIDs. To overcome this problem, we have designed and synthesized ibuprofen - antioxidant (thymol, guaiacol, eugenol, and menthol) hybrids (6-13) with and without spacer as gastro sparing agents. The hybrids have been found to be chemically stable, biolabile and exhibited retention of anti-inflammatory and analgesic activity with significant reduced ulcerogenicity as compared to the ibuprofen and ibuprofen + antioxidant physical mixture. The absence of ulcerogenicity may be attributed to antioxidants and improved physicochemical properties of these hybrid molecules.

Design, synthesis and evaluation of lantadene A congener with hydroxyl functionality in ring A as an antitumour agent.

Pentacyclic triterpenoid lantadene A congener with hydroxyl functionality in ring A was designed and synthesised on the basis of enhancement of polarity and bioactivity. The new synthesised compound 22ß-angeloyloxy-methyl-2-hydroxy-3-oxoolean-1,12-dien-28-oate (6) was screened for cytotoxicity against human cancer cell lines (HL-60, HeLa, Colon 502713 and A-549) and showed a better cytotoxicity than the parent compound (p<0.05). Further, compound 6 was screened for in vivo antitumour activity in a two-stage squamous cell carcinogenesis model, using female Swiss albino mice. Compound 6 showed a better tumour inhibition profile than the parent compound. Compound 6 also exhibited a marked decrease in protein expression of activator protein-1 (c-jun), nuclear factor-kappa B (p65) and p55. The results inferred that an increase in polarity of the lead molecule not only increased the antitumour activity but also reduced the dose, which may be linked to the deregulation of the abovementioned molecular targets, and warrants further optimisation of the structure to make it a drug-like candidate.