Bioinspired synthesis of pure massicot phase lead oxide nanoparticles and assessment of their biocompatibility,cytotoxicity and in-vitro biological properties

Green and ecofriendly route for biosynthesis of lead oxide nanoparticles has been successfully demonstrated using aqueous leaf extracts of Sageretia thea (Osbeck.). Biosynthesized PbO (∼27 nm) nanoparticles were extensively characterized using XRD, FTIR, Raman, EDS etc. Morphology was studied through HR-TEM/SEM. As synthesized nanoparticles were investigated for their iv-vitro biological properties. Antibacterial activities revealed enhancement upon modulation by UV in a concentration dependent manner. Pseudomonas aeruginosa was found to be the most resistant strain (MIC = 250 µg/mL and MIC^uv = 31.25 µg/ml). MTT cytotoxicity on leishmania promastigotes and amastigotes revealed significant inhibition as indicated by their IC₅₀ values of 14.7 µg/mL and 11.95 µg/m respectively. Cytotoxicity was also confirmed using brine shrimp lethality (IC₅₀ = 27.7 µg/mL). Bio-compatibility evaluation indicated cytotoxicity to freshly isolated human macrophages (IC₅₀ = 57.1 µg/mL). Insignificant alpha-amylase inhibition and moderate protein kinase inhibition was revealed. Antioxidant activities indicated free radical scavenging activity (58 ± 2.45) at 200 µg/mL. Moderate total reducing power and total antioxidant activity was also indicated. Overall, we conclude lead oxide as a potential candidate for biological applications, however further studies are recommended on their in vitro and in vivo cytotoxicity.     

Physical properties,biological applications and biocompatibility studies on biosynthesized single phase cobalt oxide (Co3O4) nanoparticles via Sageretia thea (Osbeck.)

Cobalt oxide nanoparticles were successfully biosynthesized by complete green process using aqueous leaf extracts of Sageretia thea as chelating agent. Diverse techniques were applied for characterization. Antibacterial (with and without UV illumination), antileishmanial, antioxidant and enzyme inhibition applications were assessed, while freshly isolated macrophages and red blood cells were used for biocompatibility studies. Good antibacterial nature and enhancement of bactericidal nature upon UV modulation is reported. Staphylococcus aureus and Escherichia coli are indicated as most susceptible bacterial strains. Significant cytotoxic potential is revealed with IC₅₀ calculated as 12.82 µg/ml and 3.16 µg/ml against the axenic leishmanial promastigote and amastigote cultures respectively. Biogenic cobalt oxide nanoparticles indicated DPPH free radical scavenging potential, while moderate antioxidant capacity and reducing power was demonstrated. Bioinspired cobalt oxide also demonstrated alpha amylase and protein kinase inhibition at higher concentrations. Biogenic cobalt oxide was found as more cytotoxic to macrophages (IC₅₀ = 58.55 µg/ml) then to RBC’s (IC₅₀ >200 µg/ml). Our results indicate green synthesis as an alternative, effective and eco-friendly method for the biosynthesis of cobalt oxide nanoparticles with numerous biological applications.     

Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities

The natural product lupeol 1 was isolated from aerial parts of Vernonia scorpioides with satisfactory yield, which made it viable to be used as starting material in semisynthetic approach. Ten lupeol derivatives 2–11 were prepared by classical procedures. Including, five new esters derivatives 7–11, which were obtained by structural modifications in the isopropylidene fragment. All semisynthetic compounds and lupeol 1–11 were confirmed by ¹H NMR, ¹³C NMR and HRMS. Their antiprotozoal activity was evaluated in vitro against L. amazonensis and T. cruzi. Derivative 6 showed the best antitrypanosomal activity (IC₅₀ = 12.48 μg/mL) and the lowest cytotoxic derivative (CC₅₀ = 161.50 μg/mL). The mechanism of action of the most active derivatives (4, 6 and 11) is not dependent from the enzyme trypanothione reductase.     

The first total synthesis of the (±)-17-methyl-trans-4,5-methyleneoctadecanoic acid and related analogs with antileishmanial activity

The first total synthesis of the marine cyclopropane fatty acid (±)-17-methyl-trans-4,5-methyleneoctadecanoic acid was accomplished in eight steps and in 9.1% overall yield starting from 1-bromo-12-methyltridecane. The cis analog (±)-17-methyl-cis-4,5-methyleneoctadecanoic acid was also synthesized but in seven steps and in 16.4% overall yield. With the two isomeric cyclopropane fatty acids at hand it was possible to unequivocally corroborate the trans relative configuration of the naturally occurring fatty acid by gas chromatographic co-elution of the corresponding methyl esters. The cis isomer was cytotoxic to Leishmania donovani promastigotes with an IC₅₀ of 300.2 ± 4.2 μM.     

Synthesis,Spectroscopy, Semi‐empirical and Biological Activities of Organotin(IV) Complexes with o‐Isopropyl Carbonodithioic Acid

New organotin(IV) complexes have been synthesized by treating potassium o‐isopropyl carbonodithioate with R₂SnCl₂/R₃SnCl in 1 : 2/1 : 1 M/L ratio. All complexes have been characterized by IR and NMR (¹H, ¹³C) spectroscopy. IR results shows that ligand acts as bidentate which is also confirmed by semi‐empirical study. NMR data reveals four coordinated geometry in solution. Computed positive heat of formation shows that complex 5 is thermodynamically unstable. UV/visible spectroscopy was used to assess the mode of interaction and binding of the complexes with DNA which shows that complex 5 exhibits higher binding constant as compared to complex 3 . In protein kinase inhibition assay, compound 3 was found most active, while other biological activities shows that triorganotin(IV) complexes are biologically more active as compared to diorganotin(IV) complexes.     

Structure determination and absolute configuration of cannabichromanone derivatives from high potency Cannabis sativa

Three new cannabichromanone derivatives were isolated from high potency cannabis, along with the known cannabichromanone. Full spectroscopic data, including the use of electronic circular dichroism and Mosher ester analysis to determine the absolute configuration of these compounds, are reported. All isolates were tested for antimicrobial, antimalarial, antileishmanial, and anti-oxidant activities.     

Synthesis and Antileishmanial Activities of Some New Azasterols

A series of novel azasterols 8a―8h and 10a―10c were synthesized from the key intermediate 6 by acylation and deprotection.Compound 6 was obtained through a series of reactions including Wittig reaction,etherification,ene reaction,oxidation,oximation and reduction.Structures of the synthesized compounds were confirmed by IR,MS and 1H NMR.Furthermore,all of these compounds were screened for in vitro antiparasitic activity against L.donovani.Among them,compounds 8h,10a and 10b showed a fair inhibition of leishmania promastigotes growth at 25 μg/mL,with potencies close to that of the reference drug,amphotericin B.The results provide a starting point for the development of novel drugs to treat leishmaniasis.     

Recent trends in the design of antimicrobial agents using Ugi-multicomponent reaction

Multi-drug resistant (MDR) forms of several bacteria, fungi, viruses, and parasites pose a serious challenge to human health and economy. Hence, the rise of antimicrobial resistance (AMR) requires the expedient discovery of novel antimicrobial agents with a unique mode of action. Ugi multicomponent reaction (Ugi-MCR) and its variants have proved to be an important tool in the hand of a medicinal chemist. Traditional Ugi reaction provides one-step access to peptide-like molecules. However, several modifications of Ugi products are now available, enabling the design of diverse molecular scaffolds. This has tremendously expanded the scope of Ugi-MCR in drug discovery. This review focuses on the recently reported application of Ugi reaction in the design of molecules against important pathogenic microbes and parasites. The design, synthesis, and bioactivities of important lead molecules from the literature is discussed. Towards the end, we also provide our perspective highlighting the overall trends in Ugi-MCR enabled antimicrobial drug design and future prospects.     

Development of a reversed FIA system for the spectrophotometric determination of Sb(III) and total Sb in antileishmanial drugs

This paper reports the development of a reversed flow injection system for the spectrophotometric determination of Sb(III) and total Sb in antileishmanial drugs. The analytical system is based on the selective reaction between Sb(III) and bromopyrogallol red (BPR) with the decrease of the absorbance at 555 nm. Total Sb concentration was determined after reduction of all Sb(V) to Sb(III) with KI and ascorbic acid. The influence of system variables (chemical and flow type) and the possible interference of high amounts of Sb(V) on Sb(III) was studied as well as the suitable conditions for preparation of samples. It was verified that the use of Triton X-100 enhanced the sensitivity of the methodology and that the previous sonication of the samples was fundamental to achieve accurate results. Under optimized conditions the reversed FIA system was able to process 63 samples per hour with a detection limit of 29 ng ml⁻¹ and a R.S.D. of 3.8% (0.25 μg ml⁻¹ level). Real samples of commercial antileishmanial drugs were analyzed, being observed no statistical difference between the results obtained by the developed system and FAAS or manual methodology in relation to total Sb concentration.     

Expeditious synthesis,antileishmanial and antioxidant activities of novel 3-substituted-4-hydroxycoumarin derivatives

A series of novel 3-substituted-4-hydroxycoumarin derivatives 6(a–1) were synthesized in high yield using one-pot three component coupling reaction catalyzed by ceric ammonium nitrate. These compounds were evaluated for antileishmanial activity against Leishmania donovani promastigotes and antioxidant activity(DPPH-radical scavenging activity). Two compounds, 6h(IC_(50)= 9.90 μmol/L) and 6i(IC_(50)= 6.90 μmol/L) displayed potent antileishmanial activity when compared with standard antileishmanial agents pentamidine(IC_(50)= 16.15 μmol/L) and miltefosine(IC_(50)= 12.50 μmol/L). Three compounds, 6c(IC_(50)= 10.79 μmol/L), 6h(IC50= 10.60 μmol/L), and 6i(IC_(50)= 10.73 μmol/L) showed significant antioxidant activity favorably with the antioxidant standards butylated hydroxy toluene(IC_(50)= 16.47 μmol/L) and ascorbic acid(IC_(50)= 12.69 μmol/L). A molecular docking study of compounds 6(a–1) suggested a possible mode of binding with the Adenine phosphoribosyltransferase enzyme of L.donovani. ADME properties were predicted in silico and support the potential of 6(a–1) to show favorable drug-like properties.