A bioinorganic chemistry perspective on the roles of metals as drugs and targets againstMycobacterium tuberculosis– a journey of opportunities

Abstract

Bioinorganic approaches in developing metallodrugs for tuberculosis are discussed, along with our understanding of key metalloproteins with drug target opportunities.

Quaternary Ru(ii) complexes of terpyridines, saccharin and 1,2-azoles: effect of substituents on molecular structure, speciation, photoactivity, and photocytotoxicity

“…(2)−40.67 (5) min in DMF and 47.24 (3)−231.00 (2) min in 2% (v/v) DMF-Tris-HCl/NaCl buffer (Table 3). The hydrolysis rates are slower than the corresponding solvolysis rates in DMF for the complexes.…”

“…Photoactivated ruthenium complexes have gained much attention in recent years to treat several pathophysiological conditions like cancer and bacterial infections. [1][2][3][4][5] Conventional chemotherapy is associated with undesirable high toxicities, poor selectivity, and drug resistance as the major clinical challenges. The clinically accepted photodynamic therapy (PDT) and recently developed photoactivated chemotherapy (PACT) are two major modalities that circumvent the significant limitations of tra-ditional chemotherapy.…”

When NO. Is not Enough: Chemical Systems, Advances and Challenges in the Development of NO. and HNO Donors for Old and Current Medical Issues

“…Pretomanid (PA‐824) and delamanid (OPC‐67683 or deltyba) (Figure 10), both a bicyclic nitroimidazole, were recentrly approved by the FDA (in 2019 and 2014, respectively) for the treatment of adult patients with extensively drug‐resistant tuberculosis (TB) in combination with other antituberculosis drugs [60] . Pretomanid and delamanid, like others nitroimidazole antibiotics, are pro‐drug that require bioactivation by the mycobacterial deazaflavin (F420)‐dependent nitroreductase (Ddn) that catalyzes their conversion to des‐nitroimidazole and NO 2 − products, this latter, through additional reduction, can generate NO .…”

“…Both INH and PYZ are anti‐tuberculosis (anti‐TB) prodrugs. Oxidation of the metal center (Fe II →Fe III ) with hydrogen peroxide (H 2 O 2 ) promoted an accelerated oxidation of the organic ligands producing the active metabolites of INH and PYZ, isonicotinoyl radical and pyrazinonic acid, respectively [60,128] . Thus, taking into account this redox metal‐mediated strategy, we synthesized new pentacyanoferrate(II) complexes using isonicotino‐ and pyrazino‐hydroxamic acid as ligands (Figure 12).…”

New nitrosyl ruthenium complexes with combined activities for multiple cardiovascular disorders

“…Those efforts resulted in promising compounds such as NAMI-A, KP1019, RAPTA-C and others, which were able to cause cell death through mechanisms distinct from platinum drugs. [21][22][23] Moreover, in the following years, several Ru-based species were synthesized exhibiting diverse therapeutic activities as antitumoral, 24,25 bactericide, [26][27][28] anti-parasitic, [29][30][31] and antiinflammatory [32][33][34] agents, revealing great potential for pharmacological application.…”