Future Journal of Pharmaceutical Sciences最新文献

Background

The biggest menace in the world today is the infection caused by pathogenic bacteria in humans, where majority of the available antibiotics fail to provide therapeutic results due to resistance. The discovery of new molecules is the need of the hour and several research groups worldwide are contributing to fight this scare. This work highlights our efforts towards discovering novel tetracycline hybrids that could serve as potent agents against several pathogenic bacterial strains causing infections. In total, ten compounds were synthesized which were chemically conjugates of Minocycline, an age-old tetracycline, and naturally occurring aldehydes and ketones available from the plant sources. Structural characterization of these compounds was done using Mass and ¹HNMR. Molecular docking was carried out in order to predict the binding affinity of these compounds to various bacterial enzymes and known protein targets and to establish the structure–activity relationships. Molecular dynamic simulation studies and in silico pharmacokinetic and toxicity prediction studies were done to determine in silico pharmacokinetics and toxicity of compounds. In-vitro antibacterial activities were done using standard protocols against gram positive bacteria like Enterococcus faecalis, Staphylococcus aureus and gram-negative bacteria like Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli.

Results

Promising results were obtained viz. compound 1,2 and 10 were found to be more potent against Staphylococcus aureus, compound 1 against Enterococcus faecalis, compound 2 and 3 against Escherichia coli, compound 7 and 8 against Pseudomonas aeruginosa and compound 7 against Klebsiella pneumoniae when compared with minocycline as standard compound.

Conclusion

All the synthesized compounds were screened for their anti-bacterial activity against gram positive and gram negative microorganisms. Amongst the ten synthesized minocycline hybrids, four minocycline hybrids exhibited potent antibacterial activity as compared to minocycline. These hybrids can serve as a promising lead compound for antibiotic drug discovery.

Background

Lead (Pb) is a heavy metal with extreme toxicity and numerous industrial uses. It produces nephrotoxicity with notable changes in renal architecture and function. The Alhagi maurorum (AM) belongs to the family Fabaceae and is native to the Middle East area. In the present study, the potential nephroprotective effects of AM in Pb-intoxicated rats were evaluated.

Results

AM methanolic extract was standardized in reference to its main phenolic compounds orientin, rutin, and quercetin. Acute oral toxicity studies indicated that the extract is safe for animals. Rats were allocated into five groups and treated for 28 days as follows: control, AM (200 mg/kg, orally), Pb (15 mg/kg, orally), Pb + AM (100 mg/kg), and Pb + AM (200 mg/kg). Pb administration markedly increased serum cystatin C, urea, creatinine levels, and urinary NAG. Pb also caused renal histopathological alterations. However, AM o-treatment ameliorated such pathological changes. In addition, AM treatment prevented Pb-induced accumulation of malondialdehyde (MDA), attenuated glutathione (GSH) depletion, and catalase (CAT) and superoxide dismutase (SOD) exhaustion. AM guarded against Pb-induced enhanced the protein expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB). Further, AM significantly prevented Pb-induced upregulation of mRNA levels of Bax and downregulation of Bcl-2. These effects were associated with increased levels of heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in renal tissue.

Conclusion

AM guards against Pb-induced nephrotoxicity in rats that involve, at least partly, the antioxidant, anti-inflammatory, and anti-apoptotic activities as well as the modulation of HO-1 and Nrf2 expression.

Background

Telmisartan and bisoprolol fumarate together are two medications that diminish arterial pressure. The current study comprises an evaluation of the proposed methodology's greenness regarding the HPLC method used to govern the medication mixture regardless of dose form A novel stability suggesting HPLC method's environmental effect was evaluated using the greenness metrics. Stress conditions comprising acidic, alkaline, oxidative, thermal, and photolytic degradation were applied for both of the medications.

Results

The RP—HPLC method employing a reversed-phase C₁₈ column with a gradient approach, the HPLC chromatography was carried out. The mobile phase consisted of acetonitrile, methanol, and phosphate buffer (60:35:5, %v/v/v), with the stationary phase being the Unisphere C₁₈ column Agela Tech. The RP-HPLC method uses UV detection at 224 nm with chromatographic purification spanning linearities of 2.5–12.5 μg/mL for bisoprolol fumarate and 40.0–200.0 μg/mL for telmisartan, correspondingly. The procedure is accurate and precise, as demonstrated by an outcome that % RSD inside the permissible range. Additionally, various stressors were introduced to the medications. The approach's green credentials with respect to solvent utilization, chemical substances, expenditure of energy, and waste formation have been verified by the greenness data collected during the evaluation. No chromatographic or spectrum impediments caused by formulation additives have been observed.

Conclusion

Bisoprolol fumarate and telmisartan could be measured simultaneously using the devised RP-HPLC method, which was simple, quick, sensitive, accurate, precise, linear, and stability indicating. The proposed approach showed ecological friendliness, robustness, sensitivity, and ease of use. As a result, the devised method could be applied to the regular quality checking of tablets and bulk medications.

Background

Paclitaxel (PAC) was the first-ever natural chemotherapeutic agent for the treatment of breast cancer. However, it has some drawbacks like low water solubility, a long half-life, an unregulated rate of discharge, etc. Thus, this research paper aimed to develop PAC-loaded nanoparticles to lessen toxicity and boost PAC's solubility in water. In this case, hyaluronic acid (HA), graphene quantum dots (GQDs), and adipic acid dihydrazide (ADH) have been combined in a unique way to suggest pH-responsive nanoconjugates that can improve the therapeutic effect of medicinal molecule PAC with fluorescence and breast cancer targeting.

Results

The investigation of the particle dimensions revealed that the majority of the particles were discovered to be between 25–50 nm. Additionally, the loading efficiency of PAC in PAC@HA-ADH-GQDs nanoconjugates was 93.56% and the release of PAC was around 70% at pH 5 and 20% at pH 7.4 in 24 h. The MTT test's risk-free methodology successfully supports the classification of HA-ADH-GQD as a biocompatible substance as it demonstrates cell viability of more than 75%. Additionally, cellular uptake research has shown that MCF7 cancer cells absorbed more PAC@HA-ADH-GQDs than GQDs alone due to the presence of targeting agent HA.

Conclusion

In this study, we have investigated the potential of the hyaluronic acid motif (HA-ADH-GQDs)-attached nanotherapeutics (NTCs) as a carrier for simultaneous fluorescence imaging and pH-triggered targeted administration of anticancer medication for the treatment of breast cancer. The suggested study is innovative since anticancer drug delivery using HA-GQDs NTCs with adhesive capabilities of ADH has not been previously described.

Graphical Abstract

Diagrammatic representation of the preparation of PAC@HA-ADH-GQDs NTCs for breast cancer targeting

Background

Sweet potato (Ipomoea batatas (L.) Lam.) is a member of the family Convolvulaceae. Much research has highlighted its variable biological actions in the treatment of many disorders. Our study focused on the quantitative analysis of two Egyptian sweet potato cultivars (Abees and A195). First, we applied proximate analysis, measured total phenolic, and flavonoid contents, performing an HPLC standardization of their ethanolic extracts using chlorogenic acid standard. Furthermore, the two cultivars were formulated as topical creams (3% w/w and 5% w/w) and evaluated for their anti-skin aging activity in a d-galactose-induced skin aging mouse model. Results revealed that both cultivars have high nutritional importance.

Results

Abees exhibited higher total phenolic and flavonoid contents than A195, while A195 contained a higher concentration of chlorogenic acid. Both cultivars showed a concentration-dependent anti-skin aging activity, with 5% Abees cream demonstrating the lowest visual skin-aging score, the highest activity of catalase (CAT) and superoxide dismutase (SOD), and the lowest concentration of malondialdehyde (MDA). Restoration of skin thickness and collagen content was observed in the 5% Abees group, while both Abees and A195 caused a noticeable concentration-dependent decrease in the skin SMAD7 expression. Decreased SMAD7 has been correlated to upregulating the TGF-β/SMAD3-induced collagen production in aged skin.

Conclusion

This study elaborates the nutritional importance, phenolic and flavonoid content and anti-skin aging activity of Abees and A195 roots and we recommend further preclinical and clinical investigations of sweet potato.

Background

The development of novel anti-microbial drugs for multidrug-resistant (MDR) is a significant challenge. This study aimed to synthesize various derivatives of (Z)-4-(2-aminothiazol-5-yl)-N-benzohydrazide (DT01-DT10) that are effective against a wide variety of anti-bacterial and antifungal pathogens.

Results

The binding energy of the compounds ranged from − 9.0 to − 10.0 kcal/mol. Molecular simulations produced a major result in improving the representation of the real biological conditions with an average RMSD of 0.110 nm. The derivatives DT03, DT04, and DT06 showed overall good anti-microbial activity at lower concentrations of 1.8 µg/ml. Compound DT03 showed significant activity against Gram-positive, Gram-negative bacteria and fungal strains, with inhibition zone diameters of 17, 19 and 16 mm, respectively. Compound DT04 showed promising anti-bacterial effects against S.mutans and C.albicans, with inhibition zone diameters of 18 and 17 mm, and moderate activity against B. cereus. Compound DT06 showed enhanced activity against P.aeruginosa.

Conclusion

The derivative 4-(2-amino-1,3-thiazol-5-yl)-N′-(Z)-(2-nitrophenyl) methylidene benzohydrazide (DT06), which contained a nitro group displayed potent activity at 1.8 µg/ml with an IC₅₀ of 50.31 and a selectivity index of 61.33.

Graphical abstract

Background

The pivotal intent of this study was to investigate the medicinal potential of synthesized nanotransferosomes utilizing Clerodendrum serratum L. hydroalcoholic extract (CS-NTs). Three batches, CS-NTs 25, CS-NTs 50, and CS-NTs 100, were formulated using the thin-film hydration approach with varying concentrations of phospholipids (soya phosphatidylcholine) at 25, 50, and 100 mg, respectively, to evaluate their efficacy against skin cancer cell lines. Several analytical approaches, such as UV/Vis spectroscopy, XRD spectra, FTIR, TEM, SEM, particle size distribution, and zeta potential analysis, were employed to assess the synthesized CS-NTs.

Results

Experimental results revealed that CS-NTs exhibited a circular shape, with average vesicle sizes approximately measured at 463.6 ± 100.5 nm, 265.5 ± 61.6 nm, and 409.6 ± 106.2 nm for CS-NTs 25, CS-NTs 50, and CS-NTs 100, respectively. Notably, biologically synthesized CS-NTs 25 offer potential anticancer benefits against B10F16 (skin cancer cell line) cells, exhibiting no signs of adverse effects. The heightened biological potential of CS-NTs can be ascribed to their unique characteristics at the nanoscale, characterized by an average vesicle size and lower polydispersity value, which facilitate augmented responsiveness and interactions with biological systems.

Conclusion

CS-NTs 25 formulated through the biogenic process using C. serratum hydroalcoholic plant root extract hold significant potential for anticancer activity.

Graphical abstract

Background

The leaves of Psidium guajava (PGAE), fruit peel of Punica granatum (PGRPE), and the bark of Careya arborea (CAE) are widely used traditional medicinal plants for treating diarrheal diseases across India. Our previous studies showed that the hydroalcoholic extracts of these plant parts inhibit the cholera toxin activity. Hence, this study is framed to investigate these extracts for anti-Vibrio cholerae activity and their ability to augment antibiotic sensitivity through a combination of in vitro and computational methods. The hydroalcoholic extracts of PGAE, PGRPE, and CAE were tested for antibacterial activity against Vibrio cholerae by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and virulence gene expression studies by reverse transcriptase-polymerase chain reaction (RT-PCR). Further, antibacterial activity in combination with selected antibiotics was performed by disk diffusion method. The possible mode of action of these extracts was predicted using docking and molecular dynamics studies on selected virulence factors of Vibrio cholerae.

Results

All three plant extracts depicted antibacterial activity at different degrees. CAE showed MIC and MBC at 1.25 mg/mL and 10 mg/mL, PGAE at 1.25 mg/mL and 5 mg/mL; and PGRPE at 2.5 mg/mL and 10 mg/mL, respectively. RT-PCR confirmed these extracts significantly inhibited the expression of virulence genes like Flagellin A (FlaA), Vibrio polysaccharide synthesis transcription regulator (VpsT), and Lux Operon (LuxO). Further, the computational studies predicted that phytocompounds of these plants pose stable interaction with AphA, AphB, and ToxT playing the key role in inhibiting the expression of virulence factors.

Conclusion

The results emphasize that these plant extracts potentially inhibit the growth of Vibrio cholerae, decrease the expression of virulence gene, and enhance the sensitivity of certain conventional antibiotics.

Background

Skin aging is a multifactorial disorder that occurs due to extrinsic and intrinsic factors, where a decrease in natural antioxidant defenses and an imbalance between molecular biomarkers occur. The current study aims to develop nanoliposomes for the dermal delivery of Hs and to investigate their effects on skin biomarkers and skin aging.

Methods

Chemical profiling performed via high-performance liquid chromatography (HPLC)/ESI‒PDA‒MS revealed enrichment in phenolic metabolite contents. Hs-nanolopeosomes were characterized for their mean size, encapsulation efficiency of Hs and ability to penetrate the skin via confocal microscopy. An aged rat model generated via UV and galactosamine injection was evaluated for reduced glutathione (GSH) and malondialdehyde (MDA) levels, in addition to the levels of collagenase and elastase enzymes in the different study groups, which included a healthy control group, an aged group, a prophylactic group, an aged group treated with Hs-nanoliposomes, and a green tea extract-treated group (positive control). Moreover, the Bcl-2/Bax proteins were determined via ELISA, and MMP-1, MMP-2, MMP-9, and TIMP-1 expression was determined via RT‒qPCR in the study groups.

Results

Hs-nanoliposomes (~ 400 nm) proved deep skin localization in confocal images. Compared with the aged group and the green tea extract-treated group, the Hs-liposome-treated group presented elevated reduced glutathione and decreased malondialdehyde levels and inhibited collagenase and elastase enzymes. This treatment also decreased the Bcl-2/Bax ratio and downregulated the expression of MMP-1, MMP-2, and MMP-9. However, upregulation of TIMP-1 expression was detected. The outcomes were confirmed by histopathological assays, which revealed reduced saging and collagen damage in the Hs-nanolipid-treated group.

Conclusion

The present study proposed a potential antiaging nanobased formulation that can deliver Hs extract deep in the dermis layer to prevent the oxidative stress that leads to aging.

Background

The recent FDA-approved Ycanth (cantharidin) for treating Molluscum contagiosum, a viral skin infection, was first reported from blister beetles. Medicinal insects are reservoirs for exploring bioactive molecules, which have various benefits. Their use in traditional medicinal practices explains why uncovering new chemical substances is worthwhile.

Main body of the abstract

Insect-derived natural products with diverse and unique structures are significant for drug discovery and development potential. Various natural products are reported from insect sources; in this context, it also emphasizes the importance of active global participation among researchers, as it offers significant potential for developing a sustainable approach to why this should not remain untouched for ever-increasing unmet challenges.

Conclusion

Hence, practitioners in natural product chemistry and allied disciplines have a role in understating the enormous potential of discovering bioactive metabolites for their medicinal value to human health.