Soroush Sardari

In vitro and in vivo anti-malarial activity of Boerhavia elegans and Solanum surattense

BackgroundThere is an urgent need to identify new anti-malarial drug targets for both prophylaxis and chemotherapy, due to the increasing problem of drug resistance to malaria parasites. In the present study, the aim was to discover novel, effective plant-based extracts for the activity against malaria.MethodsTen plants found in Iran were selected by ethnobotanical survey of medicinal plants. The crude ethanolic extracts were tested for in vitro anti-plasmodial activity against two strains of Plasmodium falciparum: K1 (chloroquine-resistant strain) and CY27 (chloroquine-sensitive strain), using the parasite lactate dehydrogenase (pLDH) assay. The anti-plasmodial activity of the extracts was also assessed in the 4-day suppressive anti-malarial assay in mice inoculated with Plasmodium berghei (ANKA strain). Crude ethanolic extracts showed good anti-plasmodial activity were further fractionated by partitioning in water and dichloromethane.ResultsOf 10 plant species assayed, three species: Boerhavia elegans (Choisy), Solanum surattense (Burm.f.) and Prosopis juliflora (Sw.) showed promising anti-plasmodial activity in vitro (IC50 ≤ 50 μg/ml) and in vivo with no toxicity. The dichloromethane fraction of three extracts revealed stronger anti-plasmodial activity than the total extracts.ConclusionAnti-plasmodial activities of extracts of B. elegans and S. surattense are reported for the first time.

Synthesis and biological evaluation of coumarin derivatives as inhibitors of Mycobacterium bovis (BCG).

The coumarin compounds are an important class of biologically active molecules, which have attractive caught the attention of many organic and medicinal chemists, due to potential pharmaceutical implications and industrial applications. We herein report the one‐pot procedure for the efficient synthesis of coumarin derivatives using commercially available substrates via isocyanide‐based multicomponent condensation reactions. These compounds were evaluated for anti‐mycobacterium activity against Mycobacterium bovis (Bacillus Calmette–Guerin). The preliminary results indicated that all of the tested compounds showed relatively good activity against the test organism. The compounds 7e, 7l, and 7m showed high anti‐tuberculosis activity.

Virtual Screening of Anti-Mycobacterial Plant Compounds.

Deaths from tuberculosis have long gripped people and threatened human health. The need for new drug compounds are critically sensed by medical scientists and practitioners due to the emergence of new strains and the slow rate of discovering novel medicines for this disease. Since plants are a rich source of diverse drug compounds, they are among the best choices to achieve new ones. The study of all plants or their compounds is an almost impossible scenario; hence bio/cheminformatics methodology can be used to reduce time and cost spent in drug discovery. For this purpose, we made several databases of anti‐mycobacterial plant compounds and further found filter criteria which were able to describe more predicted bioactive compounds by the established algorithm. Also, we present the survey of the developed resource by using bio/cheminformatics tools. The presence of several anti‐mycobacterial compounds in the predicted algorithm and introduction of new active compounds represent the high potential of this method. In addition, the general profile of such bioactive molecules is pinpointed using molecular descriptors and cheminformatics approach.

Synthesis and biological evaluation of propargyl acetate derivatives as anti-mycobacterial agents.

BackgroundThe emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has intensified efforts to discover novel drugs for tuberculosis (TB) treatment. Targeting the persistent state of Mtb, a condition in which Mtb is resistant to conventional drug therapies, is of particular interest.MethodsThis study is focused on propargyl acetate derivatives. Eight molecules were designed based on propargyl alcohols and different acid anhydrides.ResultsAll the synthesized compounds and commercially available ones were evaluated for anti-tuberculosis activity.ConclusionsInhibitors against Mtb have been identified and characterized for further development into potential novel anti-tubercular drugs.

Synthesis and antimycobacterial activity of novel thiadiazolylhydrazones of 1-substituted indole-3-carboxaldehydes.

A series of novel thiocarbohydrazones of substituted indoles and their corresponding thiadiazole derivatives were prepared, and their structures were confirmed by different analytical and spectroscopic methods. The derivatives were prepared by a sequential synthetic strategy including substitution at N‐1 position of indole ring by various aliphatic and benzylic substituents, followed by condensation with thiocarbohydrazide, and finally cyclization by triethyl orthoformate. The derivatives were tested for their antimycobacterial activity against Mycobacterium bovis BCG, and the results revealed that among the synthesized compounds, thiadiazole derivatives 4e, 4f, 4n, 4p, 4q, and 4t exhibited the highest activity with IC50 value of 3.91 μg/mL. The results indicate that the thiadiazole moiety plays a vital role in exerting antimycobacterial activity.

Design, Synthesis and Evaluation of New Azoles as Antifungal Agents: a Molecular Hybridization Approach

Two benzimidazole derivatives and one nitroimidazole derivative were designed using molecular hybridization approach. The designed compounds were synthesized and their in vitro antifungal activities were tested against Candida albicans and Saccharomyces cerevisiae strains. Based on the antifungal activity data, compound 9 containing 2-methyl-5-nitroimidazole moiety proved to be the most potent compound. It was more active than the reference drugs fluconazole and ketoconazole against S. cerevisiae.

Design and Antimicrobial Evaluation of 1-Methylimidazole Derivatives as New Antifungal and Antibacterial Agents

Azole antifungal agents, which are widely used as antifungal antibiotics, inhibit cytochrome P450 sterol 14α-demethylase (CYP51). In this research, a group of 1-methylimidazole derivatives were synthesized for evaluation as antibacterial and antifungal agents. Antimicrobial evaluation revealed that some of these compounds exhibited significant antimicrobial activities against tested pathogenic fungi and bacteria, wherein compounds 3 and 8 were most potent. To find the action mechanism, all of these compounds were subjected to docking studies using the AutoDock 4.2 program. The results show that all of the azoles (2 – 5, 7, and 8) interacted with 14α-DM, wherein azole – heme coordination, hydrogen binding, and -cation interactions were involved in the drug – receptor interaction. These studies offer some useful references in order to understand the action mechanism; moreover, performing the molecular design or modification of this series as a lead compound can assist in identifying new and potent antimicrobial agents.

The effect of structural parameters and positive charge distance on the interaction free energy of antimicrobial peptides with membrane surface

Many attempts have been made to find hints explaining the relationship between physicochemical and structural properties of antimicrobial peptides (AMPs) which are relevant to their antimicrobial activities. We here found that there is a difference in the percentages of hydrophobic, hydrophilic, and charged residues between AMPs killing both bacteria and fungi (Group A) and AMPs that only kill bacteria (Group B). The percentage of charged residues in Group A AMPs is highly elevated, while in Group B the percentage of hydrophobic residues is increased. This result suggests a sequence-based mechanism of selectivity for AMPs. Moreover, we examined how the distance between basic residues affects the interaction free energy of AMPs with the membrane surface, since most of the known AMPs act by membrane perturbation. We measured the average distance between basic residues throughout the 3D structure of AMPs by defining Dpr parameter and calculated the interaction free energy for 10 AMPs that interacted with the DPPC membrane using molecular dynamics simulation. We found that the changes of the interaction free energy correlates with the change of Dpr by a linear regression coefficient of r2 = .47 and a cubic regression coefficient of r2 = .70.

(E)-1-(2-Nitro­benzyl­idene)-4-phenyl­thio­semicarbazide

In the title molecule, C14H12N4O2S, the conformation about the imine bond is trans. The dihedral angle between the two rings is 88.22 (11)°. An intramolecular N—H⋯N contact occurs. The crystal structure features N—H⋯S and C—H⋯O hydrogen bonds.