Medicinal Chemistry

Dr Anna Tevyashova’s research relates to the search for and development of a new generation of antibiotics and antitumor agents. In addition to the widespread resistance of microorganisms, researchers have linked the complexity of chemotherapy for several infectious diseases to a lack of efficacy and adverse reactions. 

During the last few years, her research has focused on finding antifungal drug candidates. The most common fungal nosocomial infections are caused by external pathogens. This makes them difficult to avoid, because opportunistically pathogenic fungi are part of the human microflora. Current methods of preventing fungal infections remain unsatisfactory. 

Doctors use antifungals used to treat invasive fungal infections, and they can be split into four classes of drugs, two of which — polyene macrolide antibiotics and synthetic azole derivatives — target ergosterol, a component of the fungal cell membrane. Some established antifungal drugs have other targets. There is an urgent need to develop novel, highly selective drug candidates with a different mechanism of action for antifungal chemotherapy or for agricultural applications. 

Tevyashova’s future projects will focus on designing and chemically synthesizing inhibitors of enzyme pathways unique for fungal cells, such as the one involved in amino acids biosynthesis pathways and protein biosynthesis. She will evaluate the biological activity of the obtained compounds on different models including their antimicrobial activity. The obtained results will provide guides for the next high-affinity generation of inhibitors of the fungal specific enzymes, which may serve as targets for new drugs. 

Additionally, Tevyashova will develop attractive antimicrobial candidates against Gram-negative bacteria, such as Escherichia coli and Pseudomonas aeruginosa.

In her previous position as a principal investigator at the Gause Institute of New Antibiotics in Russia, Tevyashova headed up interdisciplinary projects involving the design, synthesis, and evaluation of antimicrobial and antitumor compounds. This research included coordinating preclinical studies of selected drug candidates. Her team developed two candidate compounds suitable for further clinical development — antifungal Amphamide for the treatment of systemic mycoses and antitumor drug candidate Olivamide. 

As a part of Constructor University, she plans to continue her research, focusing on the discovery and development of new potent and safe antimicrobials.

Tevyashova is currently setting up a laboratory of medicinal chemistry at Constructor University, with a focus on anti-infective drug discovery and development.

• Tevyashova A.N., Efimova S.S., Alexandrov A.I., Omelchuk O.A., Ghazy E., Bychkova E.N., Zatonsky G.B., Grammatikova N.E., Dezhenkova L.G., Solovieva S.E., Ostroumova O.S., Shchekotikhin A.E. Semisynthetic amides of Amphotericin B and Nystatin A1: A comparative study of in vitro activity/toxicity ratio in relation to selectivity to ergosterol membranes, Antibiotics, 2023, 12, 151 
• Tevyashova A.N., Efimova S.S., Alexandrov A.I., Ghazy E., Bychkova E.N., Solovieva S.E., Zatonsky G.B., Grammatikova N.E., Dezhenkova L.G., Pereverzeva E.R., Isakova E.B., Ostroumova O.S., Omelchuk O.A., Muravieva V.V., Krotova M.M., Priputnevich T.V., Shchekotikhin A.E. Semisynthetic amides of polyene antibiotic Natamycin, ACS Infect. Dis. 2023, 9, 42–55 
• Tevyashova A.N., Chudinov M.V. Progress in the medicinal chemistry of organoboron compounds. Russ. Chem. Rev., 2021, 90 (4), 451–487; 
• Beniaminov A.D., Chashchina G.V., Livshits M.A., Kechko O.I., Mitkevich V.A., Mamaeva O.K., Tevyashova A.N., Shtil A.A., Shchyolkina A.K., Kaluzhny D.N. Discrimination between G/C Binding Sites by Olivomycin A Is Determined by Kinetics of the Drug-DNA Interaction. Int. J. Mol. Sci. 2020, 21, 5299 
• Tevyashova A.N., Bychkova E.N., Solovieva S.E., Zatonsky G.V., Grammatikova N.E., Isakova E.B., Mirchink E.P., Treshchalin I.D., Pereverzeva E.R., Bykov E.E., Efimova S.S., Ostroumova O.S., Shchekotikhin A.E. Discovery of Amphamide, a Drug Candidate for the Second Generation of Polyene Antibiotics. ACS Infect. Dis. 2020, 6, 2029−2044 https://dx.doi.org/10.1021/acsinfecdis.0c00068