Antifungal, molecular docking and cytotoxic effect of the essential oil of <i>Cymbopogon citratus</i> (DC) Stapf. and <i>Cymbopogon nardus </i> (L.) Rendle against Candida albicans

PRADO, GUILHERME M.; PRADO, JÚLIO CÉSAR S.; AGUIAR, FRANCISCA LIDIANE L. DE; BARBOSA, FRANCISCO CESAR B.; VALE, JEAN P.C. DO; MARTINS, MARIA ROSÁRIO; ARANTES, SILVA MACEDO; SOUSA, NATÁLIA V. DE; LIMA, DANIELLE M.; MARINHO, EMMANUEL S.; MARINHO, MÁRCIA M.; FONTENELLE, RAQUEL O.S.

doi:10.1590/0001-3765202420230309

person GUILHERME M. PRADO

investigation of data on antifungal activities and writing—original draft preparation

schoolUniversidade Federal do Ceará, Av. Cmte. Maurocélio Rocha Pontes, 100, Jocely Dantas de Andrade Torres, 62042-250 Sobral, CE, Brazil

0000-0002-5641-6983

person JÚLIO CÉSAR S. PRADO

collected data on antifungal activities

schoolUniversidade Federal do Ceará, Av. Cmte. Maurocélio Rocha Pontes, 100, Jocely Dantas de Andrade Torres, 62042-250 Sobral, CE, Brazil

0000-0001-7662-9209

person FRANCISCA LIDIANE L. DE AGUIAR

writing—review and editing

schoolUniversidade Estadual Vale do Acaraú, Centro de Ciências Agrárias e Biológicas, Av. Padre Francisco Sadoc de Araujo, 850, Alto da Brasilia, 62010-295 Sobral, CE, Brazil

0000-0003-1733-2119

person FRANCISCO CESAR B. BARBOSA

visualization and review

schoolUniversidade Federal do Ceará, Av. Cmte. Maurocélio Rocha Pontes, 100, Jocely Dantas de Andrade Torres, 62042-250 Sobral, CE, Brazil

0000-0002-3444-6997

person JEAN P.C. DO VALE

collected data from extraction of essential oil

schoolUniversidade Estadual Vale do Acaraú, Centro de Ciências Exatas e Tecnologia, Av. Padre Francisco Sadoc de Araujo, 850, Alto da Brasilia, 62010-295 Sobral, CE, Brazil

0000-0001-5598-8886

person MARIA ROSÁRIO MARTINS

Chromatographic analyses and evaluation of chemical composition of essential oils

schoolDepartmento de Ciências Médicas e da Saúde, Universidade de Evora, Colégio Luís António Verney, Rua Romão Ramalho, 59, 7000-671 Évora, PortugalschoolHERCULES Laboratory, Instituto de Investigação e Formação Avançada (IIFA), Universidade de Evora, Palácio do Vimioso, Largo Marquês de Marialva 8, 7000-809, Evora, Portugal

0000-0002-8634-3690

person SILVA MACEDO ARANTES

Chromatographic analyses and evaluation of chemical composition of essential oils

schoolHERCULES Laboratory, Instituto de Investigação e Formação Avançada (IIFA), Universidade de Evora, Palácio do Vimioso, Largo Marquês de Marialva 8, 7000-809, Evora, Portugal

0000-0001-8779-9828

person NATÁLIA V. DE SOUSA

collected data on cytotoxic

schoolPrograma em Ciências Médicas, Universidade de Fortaleza, Centro de Ciências da Saúde, Av. da Universidade, 2853, Benfica, 60020-181 Fortaleza, CE, CEP, Brazil

0000-0002-6082-0743

person DANIELLE M. LIMA

collected data on cytotoxic

schoolPrograma em Ciências Médicas, Universidade de Fortaleza, Centro de Ciências da Saúde, Av. da Universidade, 2853, Benfica, 60020-181 Fortaleza, CE, CEP, Brazil

0000-0003-2734-6768

person EMMANUEL S. MARINHO

collected data on molecular docking

schoolPrograma de Pós-Graduação em Ciências Naturais, Universidade Estadual do Ceará/UECE, Av. Dr. Silas Munguba, 1700, 60714-903 Fortaleza, CE, Brazil

0000-0002-4774-8775

person MÁRCIA M. MARINHO

collected data on molecular docking

schoolPrograma de Pós-Graduação em Ciências Naturais, Universidade Estadual do Ceará/UECE, Av. Dr. Silas Munguba, 1700, 60714-903 Fortaleza, CE, Brazil

0000-0002-7640-2220

person RAQUEL O.S. FONTENELLE

validation and study design

schoolUniversidade Estadual Vale do Acaraú, Centro de Ciências Agrárias e Biológicas, Av. Padre Francisco Sadoc de Araujo, 850, Alto da Brasilia, 62010-295 Sobral, CE, Brazil

0000-0002-8865-5954

Correspondence to: Guilherme Mendes Prado E-mail:
guimp2105@gmail.com

Universidade Federal do Ceará, Av. Cmte. Maurocélio Rocha Pontes, 100, Jocely Dantas de Andrade Torres, 62042-250 Sobral, CE, Brazil

Universidade Estadual Vale do Acaraú, Centro de Ciências Agrárias e Biológicas, Av. Padre Francisco Sadoc de Araujo, 850, Alto da Brasilia, 62010-295 Sobral, CE, Brazil

Universidade Estadual Vale do Acaraú, Centro de Ciências Exatas e Tecnologia, Av. Padre Francisco Sadoc de Araujo, 850, Alto da Brasilia, 62010-295 Sobral, CE, Brazil

Departmento de Ciências Médicas e da Saúde, Universidade de Evora, Colégio Luís António Verney, Rua Romão Ramalho, 59, 7000-671 Évora, Portugal

HERCULES Laboratory, Instituto de Investigação e Formação Avançada (IIFA), Universidade de Evora, Palácio do Vimioso, Largo Marquês de Marialva 8, 7000-809, Evora, Portugal

Programa em Ciências Médicas, Universidade de Fortaleza, Centro de Ciências da Saúde, Av. da Universidade, 2853, Benfica, 60020-181 Fortaleza, CE, CEP, Brazil

Programa de Pós-Graduação em Ciências Naturais, Universidade Estadual do Ceará/UECE, Av. Dr. Silas Munguba, 1700, 60714-903 Fortaleza, CE, Brazil

Class	Compound	*RI _Exp.	RI _bib.	C. citratus	C. nardus
				Area (%)	Area (%)
				Mean ± _SD	Mean ± _SD
HM	β-Myrcene	990	990 ^a	2.17 ± 0.05	__
HM	Limonene	1024	1026 ^a	__	1.82 ± 0.02
HM	α-Terpinolene	1078	1076 ^b	0.23 ± 0.01	__
OM	Linalool	1096	1095 ^a	0.71 ± 0.01	0.53 ± 0.01
OM	trans-Pinocarveol	1134	1134 ^a	0.16 ± 0.01	__
OM	Isopulegol	1144	1144 ^a	0.12 ± 0.02	0.92 ± 0.01
OM	Menthone	1151	1150 ^a	0.12 ± 0.01	__
OM	Citronellal	1155	1153 ^d	__	44.44 ± 0.15
OM	Borneol	1163	1162 ^a	0.46 ± 0.01	__
OM	4-Terpineol	1175	1174 ^a	0.11 ± 0.01	__
OM	α-Terpineol	1181	1190 ^d	0.72 ± 0.03	__
OM	Myrtenal	1191	1192 ^d	0.14 ± 0.01	__
OM	Citronellol	1230	1228 ^d	__	16.97 ± 0.09
OM	Neral (Citral-b)	1241	1242 ^c	36.13 ± 0.18	__
OM	Geraniol	1257	1255 ^d	2.11 ± 0.03	26.55 ± 0.12
OM	Geranial (Citral-a)	1273	1274 ^c	48.47 ± 0.19	0.35 ± 0.01
OM	Thymol	1293	1294 ^a	0.12 ± 0.01	__
OM	Myrtenyl acetate	1330	1329 ^d	0.31 ± 0.01	__
OM	Terpinyl acetate	1338	1347 ^d	1.86 ± 0.01	0.19 ± 0.01
OM	Eugenol	1363	1358 ^d	0.78 ± 0.03	0.85 ± 0.02
HS	α-Copaene	1366	1369 ^b	0.43 ± 0.07	__
OM	Neryl acetate	1374	1363 ^d	2.40 ± 0.02	__
OM	Geranyl acetate	1382	1380 ^d	0.29 ± 0.01	0.41 ± 0.02
HS	β-Caryophyllene	1427	1417 ^a	0.17 ± 0.01	__
HS	D-Germacrene	1478	1481 ^d	__	0.33 ± 0.01
HS	γ-Cadinene	1511	1515 ^c	__	0.10 ± 0.01
OS	Elemol	1548	1548 ^d	__	3.25 ± 0.03
OS	Caryophyllene oxide	1582	1582 ^a	0.11 ± 0.01	__
OS	α-Cadinol	1653	1652 ^d	__	0.63 ± 0.01
Total identified				98.12 ± 0.74	97.47 ± 0.53

C. albicans strains*	Source	Cymbopogon citratus	Cymbopogon nardus
C. albicans strains*	Source	MIC (µg/ mL )	MIC (µg/ mL )
LABMIC 0102	Hemoculture	78.12	312.50
LABMIC 0104	Tracheal aspirate	78.12	312.50
LABMIC 0105	Hemoculture	78.12	312.50
LABMIC 0125	Diabetic foot	156.25	625.00
LABMIC 0127	Diabetic foot	78.12	625.00
ATCC 90028	ATCC, EUA	156.25	625.00

Strains	Cymbopogon citratus			Amphotericin B		FICI	Effect
	MIC μg/mL (Individual)	MIC μg / mL (Combined)		MIC μg / mL (Individual)	MIC μg / mL (Combined)
LABMIC0102	78.12	9.77		1	0.125	0.25	Synergistic
LABMIC0105	78.12	2.44		1	0.125	0.16	Synergistic
ATCC 90028	156.25	9.77		1	0.250	0.31	Synergistic
	Cymbopogon nardus			Amphotericin B
	MIC μg/mL (Individual)		MIC μg/mL (Combined)	MIC μg/mL (Individual)	MIC μg/mL (Combined)
LABMIC0102	312.5		78.125	1	0.25	0.5	Synergistic
LABMIC0105	312.5		39.0625	1	0.25	0.375	Synergistic
ATCC 90028	625		78.125	1	0.25	0.375	Synergistic

Compound	Residue	AA	Distance (Å)	Interaction
Caryophyllene oxide	205B	Gly	2.80	Hydrogen bonds
Caryophyllene oxide	261B	Thr	3.30	Hydrophobic
Caryophyllene oxide	330A	Val	3.72	Hydrophobic
Citronelal	162A	Ala	3.78	Hydrophobic
Citronelal	257B	Lys	3.52	Hydrophobic
Citronelal	281A	Phe	3.70	Hydrophobic
Citronelal	312A	Arg	2.77	Hydrogen bonds
Citronelol	260B	Gly	2.78	Hydrogen bonds
Citronelol	261B	Thr	3.82	Hydrophobic
Elemol	256A	Cys	2.83	Hydrogen bonds
Elemol	257A	Lys	3.71	Hydrophobic
Elemol	282A	Gln	3.36	Hydrophobic
Eugenol	257B	Lys	3.75	Hydrophobic
Eugenol	281A	Phe	3.79	Hydrophobic
Geranial	281A	Phe	3.71	Hydrophobic
Geranial	162 A	Ala	3.99	Hydrophobic
Geranial	281 A	Phe	3.73	Hydrophobic
Geranial	297 A	Arg	3.53	Hydrophobic
Geranial	598 B	Lys	3.65	Hydrophobic
Geraniol	257B	Lys	4.00	Hydrophobic
Geraniol	281A	Phe	3.74	Hydrophobic
Geraniol	282A	Gln	2.38	Hydrogen bonds
Geraniol	309A	Asn	3.74	Hydrophobic
Germacrene D	261B	Thr	3.11	Hydrophobic
Germacrene D	330A	Val	3.77	Hydrophobic
Isopulegol	257B	Lys	3.79	Hydrophobic
Isopulegol	278A	Glu	1.84	Hydrogen bonds
Isopulegol	281A	Phe	3.75	Hydrophobic
Isopulegol	312A	Arg	2.53	Hydrogen bonds
Limonene	162A	Ala	3.72	Hydrophobic
Limonene	257B	Lys	3.56	Hydrophobic
Linalol	329A	Pro	3.77	Hydrophobic
Linalol	330A	Val	1.95	Hydrogen bonds
Linalol	332A	Tyr	3.58	Hydrophobic
Linalyl acetate	162 A	Ala	3.95	Hydrophobic
Linalyl acetate	222 A	Thr	3.73	Hydrophobic
Linalyl acetate	281A	Phe	3.51	Hydrophobic
Linalyl acetate	598B	Lys	3.64	Hydrophobic
Linalyl acetate	297A	Arg	5.14	Salt bridges
Neral	162A	Ala	3.68	Hydrophobic
Neral	257B	Lys	3.64	Hydrophobic
Neral	281A	Phe	3.85	Hydrophobic
Neral	329A	Pro	3.85	Hydrophobic
Neral	330A	Val	3.85	Hydrophobic
Neral	602B	Thr	3.86	Hydrophobic
Neral	601B	Gly	2.73	Hydrogen bonds
Terpenyl acetate	179B	Tyr	3.06	Hydrogen bonds
Terpenyl acetate	183B	Leu	3.90	Hydrophobic
Terpenyl acetate	317B	Val	3.73	Hydrophobic
Terpenyl acetate	319B	Asn	2.85	Hydrogen bonds
Terpenyl acetate	322B	Asp	3.17	Hydrogen bonds
Terpenyl acetate	324B	Lys	3.87	Hydrophobic
Terpenyl acetate	598B	Lys	3.57	Hydrophobic
Terpenyl acetate	312A	Arg	2.46	Hydrogen bonds
α-cadinene	261B	Thr	3.47	Hydrophobic
α-cadinene	329A	Pro	3.57	Hydrophobic
α-cadinene	330A	Val	3.61	Hydrophobic
α-cadinene	332A	Tyr	3.77	Hydrophobic
β-Myrcene	222A	Thr	3.81	Hydrophobic
β-Myrcene	223A	Ile	3.91	Hydrophobic
β-Myrcene	297A	Arg	3.79	Hydrophobic
β-Myrcene	309A	Asn	3.82	Hydrophobic
β-Myrcene	598B	Lys	3.82	Hydrophobic
γ-cadinene	329A	Pro	3.66	Hydrophobic
Amphotericin B*	289A	Lys	3.78	Hydrophobic
Amphotericin B*	393B	Trp	3.46	Hydrophobic
Amphotericin B*	622B	Phe	3.64	Hydrophobic
Amphotericin B*	627B	Thr	3.52	Hydrophobic
Amphotericin B*	394B	Arg	2.08	Hydrogen bonds
Amphotericin B*	566B	Tyr	2.50	Hydrogen bonds
Amphotericin B*	586B	Asp	2.20	Hydrogen bonds
Amphotericin B*	587B	Ser	2.96	Hydrogen bonds
Amphotericin B*	588B	Ala	2.71	Hydrogen bonds
Amphotericin B*	625B	Tyr	3.10	Hydrogen bonds
Amphotericin B*	627B	Thr	2.87	Hydrogen bonds
Amphotericin B*	50A	Lys	4.57	Salt bridges
Amphotericin B*	225A	Tyr	3.61	Hydrophobic
Amphotericin B*	250A	Lys	3.84	Hydrophobic
Amphotericin B*	250A	Lys	4.27	Salt bridges
Amphotericin B*	232A	Arg	3.20	Hydrogen bonds
Amphotericin B*	299A	Arg	5.22	Salt bridges
Amphotericin B*	300A	Glu	2.23	Hydrogen bonds
Fluconazole*	671B	Val	3.44	Hydrophobic
Fluconazole*	202A	Asn	2.57	Hydrogen bonds
Fluconazole*	205A	Gly	3.20	Hydrogen bonds
Fluconazole*	261A	Thr	2.93	Hydrogen bonds
Fluconazole*	522B	Ser	2.40	Hydrogen bonds
Fluconazole*	619B	Glu	3.23	Halogen bonds
Fluconazole*	257B	Lys	3.93	Hydrophobic
Fluconazole*	284A	Tyr	3.03	Hydrogen bonds

[tfnI] *RI _Exp. - Retention index relative to C8–C22 n-alkanes on the Zebron ZB5HT Inferno™ apolar column.

^a Retention index reported by Arantes et al. (2019).

^b Retention indices reported by Videira et al. (2013).

^c Retention indices reported by Pandur et al. (2022).

^d Retention indices reported by Babushok et al. (2011).

Antifungal, molecular docking and cytotoxic effect of the essential oil of Cymbopogon citratus (DC) Stapf. and Cymbopogon nardus (L.) Rendle against Candida albicans