Elene Kalandia

  When the target undergoes a mutation and the old drugs no longer work, then it is necessary to create new potentially biologically active compounds, only a few of which can become the "final" product. Given the urgency of the topic, the aim of our work was to combine such heterocyclic fragments as: coumarin and imidazole into one molecule. Resulting in increased biological activity of the obtained compound. Because it is known that both of them are characterized by a wide range of physiological activity, for example: antiviral, anticancer, anti-cardiovascular disease, antimicrobial, antibacterial, antiinflammatory, etc. As a result of the work, a tricyclic condensed heterocyclic system was obtained and its derivatives:. 4 new compounds were also obtained, which are not yet described in the literature;. They have been characterized, refinement methods have been obtained. The obtained 8 H-imidazole [6,7-f] - coumarin is a basic compound and on its basis it is possible to obtain numerous derivatives and study their physico-chemical properties. From a scientific point of view, the novelty is the synthesis of 6 new compounds, 4 of which are obtained directly during the gradual "addition" process of the heterocyclic system. One of two, is a tricyclic condensed system and the other is its derivative. We studied their physico-chemical characteristics. Also very important is the fact that the compounds we synthesize satisfy the "Lipinski rule’’. Optimal preparatory methods for obtaining original compounds have been developed. The structure of the obtained key compound - 6-benzamido-7-nitrocoumarin is confirmed by physico-chemical methods.

The semi-empirical quantum-chemical AMI method investigates the ability of 3-nitrodibenzothiophene to form complexes with metals. The energy, electronic and structural properties of the molecule are calculated, both in the gas phase and in different solvents with different values of dielectric permeability. By analyzing the electron density of atoms in a 3-nitrodibenzothiophene molecule and analyzing their effective charges, bond angles, bond lengths, and bond sequences, nitrogen and sulfur molecules could not provide electron pairs that could form co-donor-acceptor bonds and form non-acceptor bonds. The picture is different for oxygen atoms, where high values of negative effective charge, analysis of bond lengths. Bond lengths between atoms indicate that both oxygen atoms are in the SP hybrid state and have the ability to provide electron pairs and generate donor-acceptor bonds. Therefore, in the 3-nitrodibenzothiophene molecule, nitrogen and sulfur atoms must either interact weakly with metal ions or have no interaction at all, and only oxygen atoms must possess significant electron-donor properties and the ability to bond with metal to form a four-membered metal cycle. 

In medical practice, imidazole and triazole-containing compounds are used as a wide range of therapies. They have multifaceted biological activity. For example: fungicidal, anti-inflammatory, analgesic, anticancer, antiviral, etc. In order to further increase the biological activity of heterocycles, they are combined into a single molecule. O-diamines are required to obtain tetracyclic compounds. The place of annulment of imidazole / triazole cycles depends on the configuration of the amino group in the diamines. Our goal was to get 1, 2 and 2, 3-diamino-dibenothiophen-5,5-dioxide. Isomeric tetracyclic systems are obtained from diamines. And from these diamines is formed the cycle of imidazole and triazole, by the modified Phillips method. The structures of the obtained original compounds were confirmed byinfrared, mass spectroscopy and elemental analysis.

Chemical modifications of known biologically active molecules are being developed to create new therapies. The aim of our work was to obtain tetracyclic condensate systems that would combine two bicyclic systems: benzothiophene and benzimidazole. New heterocyclic systems are obtained from 3,4-diaminodibenzothiophene using a modified Philips reaction: 1H-benzimidazole- [e] -benzothiophene; 1H-benzimidazole- [f] -benzothiophene; 1H-benzimidazole- [g] -benzothiophene. The most available derivatives of heterocyclic systems are 1,2-diaminodibenzothiophene and its derivatives 1H-benzimidazole- [e] -benzothiophene. Melting of 1,2-diaminodibenzothiophene chloride with urea and thiosaccharide yields 2-benzimidazolone- [e] -benzothiophene. 1H-Benzimidazole- [e] - Ethyl iodide was used as the alkylating agent for the alkylation of benzothiophene. By mixing the obtained compound with sulfur, 1-ethylthiobenzimidazolone- [e] -benzothiophene was obtained.

One of the main directions in the search for new drugs is the synthesis of biologically active compounds. The present work impliescombination of biological active fragments such as benzimidazole and benzotriazole on the one side and benzothyophenedioxide on the other side into one molecule. As a result of original combination of above mentioned heterocyclic fragment, change of biological activity intensity and/or direction is possible. A the initial compounds have been used dibenzothiophenedioqside. From tetraamino-dibenzothiophene-dioxide, by (Philips reaction) the action of 31%HCl and sodium nitrite have been received 4 new pentacyclic systems: 3H,7H-diimidazole[4,5-b][5,4-g]dibenzothiophene-5,5-dioxide, 3H,7H-ditriazole[4,5-b][5,4-g]dibenzothiophene-5,5-dioxide, : 3H,8Hdiimidazole[4,5-a][5,4-h]dibenzothiophene-11,11-dioxide, 3H,8H-ditriazole[4,5-a][5,4-h]dibenzothiophene-11,11-dioxide.Some derivative of synthesized systems have been received: 2,8-diacyl-3H,-7H-diimidazole[4,5-b][5,4-g]dibenzothiophene-5,5-dioxide; 3,7-diacyl-3H,-7H-ditriazole[4,5-b][5,4-g]dibenzothiophene-5,5-dioxide; 2,9-dibenzoyl-3H,-8H-diimidazole[4,5-a][5,4-h]dibenzothiophene-11,11-dioxide. Have been developed optimal instrumental methods of receiving original compounds. The structure of received synthesized compounds has been approved using IR, UV-1H-NMR spectroscopy and mass spectrometry.

It is well-known fact that among the methods of creating new remedies, chemical modification of the physically active molecule is one of the most important approach. Chemical modification also means the unification of biologically active molecules in one molecule which in most cases is followed by the change in intensity or spectrum in biological activity. The subject of our scientific research is to create condensed pentacyclic heterocyclic systems which will unite the molecules of imidazole, triazole and dibenzothiophene. Such heterocyclic systems aren’t described yet and thus are interesting from the point of view of biological activity. Moreover, each heterocycle is characterized by quite a high level of biological activity.

   The goal of our work is to get heterocycles, benzothiophene-benzimidazole and benzothiophene-benzotriazole from 1,2-diaminodibenzothiophene. Pentacyclic heterocyclic systems among them.

  The goal of the work is to create condensed heterocyclic systems, wich contain two bicyclic fragments: benzotriazole and benzo(b)thiophene/furan, each component has high biological activity. Nowadays triazoles and its derivatives are more actual. Amino triazoles are used in medicine and photography. On the base of triazoles are obtained herbicides of high acrivity and fungicides. It’s determined, that the most of triazoles class representatives have high biological activity. That’s why they are useful to produce new medicines and substances for plant protection. The initial substance were o-diamines of all possible configuration of dibenzothiophene and dibenzofuran. By cyclisation of these substances with sodium nitrite in acid area, were obtained the respective benzo(b)thiophene/furanobenzotriazoles.

   At the same time, we regard as the subject of our interest to obtain heterocyclic systems, including as imidazole and triazole, also dibenzothiophene/dibenzofuran. At the first phase we’ve taken benzo(b)thiophene/furan-benzimidazole, by treatment o-diamines of benzo(b)thiophen/furan benzimidazole of diamines with sodium nitrite in acid area, we’ve got the condensed   pentacyclic systems, containing benzimidazole and triazole. 

Doctoral Thesis Referee

Master Theses Supervisor

Doctoral Thesis Supervisor/Co-supervisor

Scientific editor of monographs in foreign languages

Scientific editor of a monograph in Georgian

Editor-in-Chief of a peer-reviewed or professional journal / proceedings

Review of a scientific professional journal / proceedings

Member of the editorial board of a peer-reviewed scientific or professional journal / proceedings

Participation in a project / grant funded by an international organization

Participation in a project / grant funded from the state budget

Patent authorship

Membership of the Georgian National Academy of Science or Georgian Academy of Agricultural Sciences

Membership of an international professional organization

Membership of the Conference Organizing / Program Committee

National Award / Sectoral Award, Order, Medal, etc.

Honorary title

Monograph

Handbook

Research articles in high impact factor and local Scientific Journals

Publication in Scientific Conference Proceedings Indexed in Web of Science and Scopus