Editorial Current Topics in Medicinal Chemistry, 2020, Vol. 20, No.

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EDITORIAL

New Developments in the Medicinal Chemistry Targeting Drug-Resistant

Infection – Part-II
Infections resistance is a global phenomenon that has led to the death of
millions of people worldwide. Despite this, therapeutic options for the
treatment of these infections are increasingly restricted. For example, only
two new classes of antibiotics have been identified and released in the market
in the last 20 years (lipopeptides and oxazolidinones). The scenario is even
worse as these new classes are to treat infections caused by Gram-positive
bacteria whereas the latest antibiotics commercialized for infections caused
by Gram-negative bacteria were described in the 1960s. In this sense, fungi
are also an important group of pathogens even though fungal infections are
L.S.M. Forezi
neglected by the public health and global health communities. Candida spp.
are the most common cause of fungal infections in humans and are classified by the U.S. Centers for
Disease Control and Prevention (CDC) as a serious threat to human health due to its increasing
resistance to antifungal drugs. Antiviral drug resistance is an increasing concern in
immunocompromised patient populations, where ongoing viral replication and prolonged drug
exposure lead to the selection of resistant strains. Rapid diagnosis of resistance can be made by
associating characteristic viral mutations with resistance to various drugs. The emergence of viral
resistance against any specific and potent drug is virtually inevitable. There is an urgent need to clarify
the most effective use of antiviral resistance assays in clinical practice.
This special issue was divided into two parts and, in this 2nd part, 6 manuscripts were selected deal-
ing with recent advances application of some compounds as sulfonamides, quinones, pyrimidines, quinolones and inhibitors of
dipeptidyl peptidase-4 in the treatment of drug-resistant infection.
de Oliveira et al. [1] investigated the antioxidant and antibacterial potential of sulfonamides derived from carvacrol, a small
molecule with druglike properties. Most sulfonamides had antioxidant and antibacterial potential, especially compound S-6,
derived from beta-naphthylamine. To understand the possible mechanisms of action involved in biological activity, the experi-
mental results were compared with molecular docking data, for an appropriate discussion on the identified structure-activity
relationships.
de Oliveira et al. [2] showed the investigation of the antioxidant and antifungal behavior of dimeric naphthoquinones de-
rived from lawsone evaluated against seven fungal strains. The antioxidant potential was tested using the combination of the
methodologies: reducing power, total antioxidant capacity and cyclic voltammetry. Molecular docking studies (PDB ID 5V5Z
and 1EA1) were conducted which allowed the derivation of structure-activity relationships (SAR). The compound 3-
methylfuran-2-carbaldehyde showed the highest antifungal potential with an emphasis on the inhibition of Candida albicans
species (MIC 0.5 µg/mL) and the highest antioxidant potential.
Leite et al. [3] described the synthesis of a series of 1H-indole-4,7-dione derivatives in good yields by reaction between
bromoquinone and β-enamino ketones copper(II)-mediated. Several indolequinone compounds showed an effective antimicro-
bial profile against Gram-positive (MIC 16 µg.mL-1) and Gram-negative bacteria (MIC 8 µg.mL-1) similar to antimicrobi-
als present in the market, in vitro antimicrobial evaluation, and in silico analysis. These results highlighted 3-acetyl-1-(2-
hydroxyethyl)-1H-indole-4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating
bacterial infections.
Pantaleão et al. [4] reported a study that investigated the main interactions between DPP-4 and a set of inhibitors, as well as
to propose potential candidates to inhibit this enzyme for the treatment of type II diabetes mellitus. For this, the authors per-
formed molecular docking studies followed by the construction and validation of CoMFA and CoMSIA models. The informa-
tion provided from these models was used to aid in the search for new candidates to inhibit DPP-4 and in the design of new
bioactive ligands from structural modifications in the most active molecule of the studied series. From the protocol employed in
this study, they were able to propose a set of analogs with biological activity predicted by the CoMFA and CoMSIA models,
suggesting that our protocol can be used to guide the design of new DPP-4 inhibitors as drug candidates to treat diabetes.
Pimentel et al. [5] could predict that PAP derivatives can be further exploited because they may provide highly selective
ATP-competitive TKIs that are active in the nanomolar or picomolar range. Thus, the ATP-binding site of PTKs is an attractive
target for the design of anticancer drugs. As a result, many TKIs with interesting in vitro and in vivo profiles are undergoing
preclinical and clinical evaluation and are expected to enter the market in the coming years.
Batalha et al. [6] provide a compilation of some of the major studies published in recent years showing the discovery and/or
development of new antiviral oxoquinoline agents, highlighting, whenever possible, their mechanisms of action.

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172 Current Topics in Medicinal Chemistry, 2020, Vol. 20, No. 3 Editorial

All these publications (part 1 and 2) confirm the importance of new developments in the medicinal chemistry targeting
drug-resistant infection.

REFERENCES
[1] de Oliveira, A.S.; de Souza, L.F.S.; Nunes, R.J.; Johann, S.; Palomino-Salcedo, D.L.; Ferreira, L.L.G.; Andricopulo, A.D. Antioxidant and antibacte-
rial activity of sulfonamides derived from carvacrol: a structure-activity relationship study. Curr. Top. Med. Chem., 2020, 20(3), 173-181.
[2] de Oliveira, A.S.; Palomino-Salcedo, D.L.; Zapp, E.; Brondani, D.; Hoppe, T.D.; Brondani, T.D.; Meier, L.; Johann, S.; Ferreira, L.L.G.; Andri-
copulo, A.D. Molecular docking and quantum studies of Lawsone dimers derivatives: New investigation of antioxidant behavior and antifungal activ-
ity. Curr. Top. Med. Chem., 2020, 20(3), 182-191.
[3] Leite, T.O.C.; Novais, J.S.; de Carvalho, B.L.C.; Ferreira, V.F.; Miceli, L.A.; Fraga, L.; Abrahim-Vieira, B.; Rodrigues, C.R.; Figueiredo, A.M.S.;
Castro, H.C.; Cunha, A.C. Synthesis, in vitro and in silico studies of indolequinone derivatives against clinically relevant bacterial pathogens. Curr.
Top. Med. Chem., 2020, 20(3), 192-208.
[4] Pantaleão, S.Q.; Philot, E.A.; Almeida, M.O.; Lima, A.N.; de Sairre, M.I.; Scott, A.L.; Honorio, K.M. Integrated protocol to design potential inhibi-
tors of dipeptidyl peptidase-4 (DPP-4). Curr. Top. Med. Chem., 2020, 20(3), 209-226.
[5] Pimentel, L.C.F.; Cunha, A.C.; Hoelz, L.V.B.; Canzian, H.F.; Marinho, D.I.L.F.; Boechat, N.; Bastos, M.M. Phenylamino-pyrimidine (PAP) privi-
leged structure: synthesis and medicinal applications. Curr. Top. Med. Chem., 2020, 20(3), 227-243.
[6] Batalha, P.N.; Forezi, L.S.M.; Tolentino, N.M.C.; Sagrillo, F.S.; de Oliveira, V.G.; de Souza, M.C.B.V.; Boechat, F.C.S. 4-Oxoquinoline derivatives
as antivirals: A ten years overview. Curr. Top. Med. Chem., 2020, 20(3), 244-255.

Fernando de Carvalho da Silva Luana da Silva Magalhães Forezi

(Guest Editor) (Guest Editor)
Current Topics in Medicinal Chemistry Current Topics in Medicinal Chemistry
Universidade Federal Fluminense Universidade Federal Fluminense
Instituto de Química Instituto de Química
Campus do Valonguinho Campus do Valonguinho
24020-150 Niterói, RJ 24020-150 Niterói, RJ
Brazil Brazil
E-mail: fcsilva@id.uff.br E-mail: luanaforezi@id.uff.br

Vitor Francisco Ferreira

(Guest Editor)
Current Topics in Medicinal Chemistry
Universidade Federal Fluminense
Departamento de Tecnologia Farmacêutica
Faculdade de Farmácia
Niterói, RJ, 24241-002
Brazil
E-mail: vitorferreira@id.uff.br