Cap 2.

Supermolecules as antibacterial agents In the past two decades the frequencies and types of lifethreatening infections have increased, especially in recent years the high incidence of multidrug-resistant (MDR), they have broken out the last line of defense of vancomycin as antibacterial drug of last report for the treatment of MDR. The synthetic antibacterial agents being used extensively in clinic, such as quinolones and sulfonamides, and antibiotics such as -Lactam antibiotics and aminoglycoside antibiotics could not inhibit effectively these bacterial strains, even the oxazolidinon with new mode of action, emerging in the past ten years, can not meet clinical needs. It is quite urgent to develop novel antibacterial agents with new mechanism of action and effectively decrease drug-resistant strains. In recent years, many investigations have proved that the complexes of antibiotics or potent antibacterial agents with various kinds of metal ions enhanced its activity and in some cases, the complexes possessed even more healing properties than the parent drugs. Therefore, to develop and screen new therapeutic antibacterial agents from these active supermolecules will be extensively investigated. According to the structures of the ligands, the supermolecules as antibacterial agents can be divided into the following parts: quinolones, sulfanilamides, schiff bases, thiosemicarbzzides and macrocycles. Supermolecule cu actiune antibacteriala n ultimele dou decenii, frecvenele i tipurile de infectii care pun viata in pericol au crescut, mai ales n ultimii ani incidena ridicat a multidrogurilor-rezistente (MDR), au izbucnit ultima linie de aprare a vancomicinei ca medicament antibacterian conform ultimului raport, pentru tratament de MDR. Agenii antibacterieni de sintez, fiind utilizati pe scar larg n clinici, cum ar fi chinolone i sulfonamide, i antibiotice, cum ar fi antibiotice -lactamice i antibiotice aminoglicozide nu pot inhiba eficient aceste tulpini bacteriene, chiar si oxazolidinon cu noul mod de aciune, n curs de dezvoltare n ultimii zece ani , nu poate satisface necesitile clinice. Este destul de urgent dezvoltarea noilor agenti antibacterieni cu mecanism nou de aciune i reducerea n mod eficient al consumului de medicamente cu tulpini rezistente. n ultimii ani, investigaiile au demonstrat c multe complexe de antibiotice sau de ageni antibacterieni puternici, cu diferite tipuri de ioni metalici au mbuntit activitatea i, n unele cazuri, complexele posed proprieti de vindecare chiar mai mult dect medicamentele mam. Prin urmare, pentru a dezvolta i ecran de noi agenti terapeutici antibacterieni din aceste supermolecule active vor fi pe larg investigati. n conformitate cu structurile de liganzi, a supermoleculelor ca ageni antibacterieni pot fi mprite n urmtoarele pri: chinolone, sulfanilamides, baze Schiff, thiosemicarbzzides i macrocicluri.

4.3 Schiff base-based supermolecules as antibacterial agents The metal complexes containing oxygen and nitrogen donor schiff bases possess unusual configuration and structural lability, and they are sensitive to molecular environment. The environment around the metal center, for example, coordination geometry, number of coordinated ligands and their donor groups, is the key factor for metalloprotein to carry out specific physiological functions. The schiff base, containing phenolic hydroxyl group or

aromatic heterocycle with three nitrogen atoms, phosphoric acid and phosphonate ester as well as their corresponding metal complexes showed significant antibacterial activities which received considerable attention. Supermolecule bazate pe baze Schiff ca agenti antimicrobieni Complexele metalice cu coninut de oxigen i azot donor bazele Schiff posed configuraie neobinuit i labilitate structurala, iar acestea sunt sensibile la mediul molecular .Mediul din jurul centrului de metal, de exemplu, geometria de coordonare, numrul de liganzi coordonati i grupurile lor donoare, este factorul cheie pentru metalloproteina pentru a efectua funcii fiziologice specifice. Baz Schiff, conine grupul de hidroxil fenolic sau heterocicluri aromatice cu trei atomi de azot, acid fosforic i esterul fosfonat, precum si complexele lor corespunztoare de metal au activiti semnificative antibacteriene, care au primit o atenie considerabil. The complex of schiff base hydrazone containing quinolines 83 showed more effective antibacterial activity. Transition metal complexes of hydrazides and sulfonamides also were found to be used as chemotherapy. Complexul de baz Schiff hydrazone conine quinolines care au artat ca au o activitate antibacteriala mai buna. Complexe de metal de tranziie de hydrazides i sulfonamide, de asemenea, s-au dovedit a fi utilizat ca chimioterapie.