<i>In Vitro</i> and <i>In Silico</i> Approaches for the Antileishmanial Activity Evaluations of Actinomycins Isolated from Novel <i>Streptomyces smyrnaeus</i> Strain UKAQ_23
Leishmaniasis, a Neglected Tropical Parasitic Disease (NTPD), is induced by several <i>Leishmania</i> species and is disseminated through sandfly (<i>Lutzomyia longipalpis</i>) bites. The parasite has developed resistance to currently prescribed antileishmanial drugs, and it...
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doaj-390ef6ec61e5409aa41b8a256aa7d8092021-08-26T13:27:47ZengMDPI AGAntibiotics2079-63822021-07-011088788710.3390/antibiotics10080887<i>In Vitro</i> and <i>In Silico</i> Approaches for the Antileishmanial Activity Evaluations of Actinomycins Isolated from Novel <i>Streptomyces smyrnaeus</i> Strain UKAQ_23Kamal A. Qureshi0Ibrahim Al Nasr1Waleed S. Koko2Tariq A. Khan3M. Qaiser Fatmi4Mahrukh Imtiaz5Riaz A. Khan6Hamdoon A. Mohammed7Mariusz Jaremko8Abdul-Hamid Emwas9Faizul Azam10Avinash D. Bholay11Gamal O. Elhassan12Dinesh K. Prajapati13Faculty of Biosciences and Biotechnology, Invertis University, Bareilly 243123, UP, IndiaDepartment of Biology, College of Science and Arts, Qassim University, Unaizah 51911, Qassim, Saudi ArabiaDepartment of Science Laboratories, College of Science and Arts, Qassim University, Ar Rass 51921, Qassim, Saudi ArabiaDepartment of Clinical Nutrition, College of Applied Health Sciences, Qassim University, Ar Rass 51921, Qassim, Saudi ArabiaDepartment of Biosciences, COMSATS University Islamabad, Islamabad 45600, PakistanDepartment of Biosciences, COMSATS University Islamabad, Islamabad 45600, PakistanDepartment of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah 51452, Qassim, Saudi ArabiaDepartment of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraydah 51452, Qassim, Saudi ArabiaBiological and Environmental Sciences and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Makkah, Saudi ArabiaCore Labs, King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Makkah, Saudi ArabiaDepartment of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah 51911, Qassim, Saudi ArabiaDepartment of Microbiology, KTHM College, Savitribai Phule Pune University, Nashik 422002, MS, IndiaDepartment of Pharmaceutics, Unaizah College of Pharmacy, Qassim University, Unaizah 51911, Qassim, Saudi ArabiaFaculty of Biosciences and Biotechnology, Invertis University, Bareilly 243123, UP, IndiaLeishmaniasis, a Neglected Tropical Parasitic Disease (NTPD), is induced by several <i>Leishmania</i> species and is disseminated through sandfly (<i>Lutzomyia longipalpis</i>) bites. The parasite has developed resistance to currently prescribed antileishmanial drugs, and it has become pertinent to the search for new antileishmanial agents. The current study aimed to investigate the <i>in vitro</i> and <i>in silico</i> antileishmanial activity of two newly sourced actinomycins, X<sub>2</sub> and D, produced by the novel <i>Streptomyces smyrnaeus</i> strain UKAQ_23. The antileishmanial activity conducted on promastigotes and amastigotes of <i>Leishmania major</i> showed actinomycin X<sub>2</sub> having half-maximal effective concentrations (EC<sub>50</sub>), at 2.10 ± 0.10 μg/mL and 0.10 ± 0.0 μg/mL, and selectivity index (SI) values of 0.048 and 1, respectively, while the actinomycin D exhibited EC<sub>50</sub> at 1.90 ± 0.10 μg/mL and 0.10 ± 0.0 μg/mL, and SI values of 0.052 and 1. The molecular docking studies demonstrated squalene synthase as the most favorable antileishmanial target protein for both the actinomycins X<sub>2</sub> and D, while the xanthine phosphoribosyltransferase was the least favorable target protein. The molecular dynamics simulations confirmed that both the actinomycins remained stable in the binding pocket during the simulations. Furthermore, the MMPBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) binding energy calculations established that the actinomycin X<sub>2</sub> is a better binder than the actinomycin D. In conclusion, both actinomycins X<sub>2</sub> and D from <i>Streptomyces smyrnaeus</i> strain UKAQ_23 are promising antileishmanial drug candidates and have strong potential to be used for treating the currently drug-resistant leishmaniasis.https://www.mdpi.com/2079-6382/10/8/887actinomycin X<sub>2</sub>actinomycin D<i>in silico</i> molecular modelingKala-azarleishmaniasismolecular dynamics simulation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kamal A. Qureshi Ibrahim Al Nasr Waleed S. Koko Tariq A. Khan M. Qaiser Fatmi Mahrukh Imtiaz Riaz A. Khan Hamdoon A. Mohammed Mariusz Jaremko Abdul-Hamid Emwas Faizul Azam Avinash D. Bholay Gamal O. Elhassan Dinesh K. Prajapati |
spellingShingle |
Kamal A. Qureshi Ibrahim Al Nasr Waleed S. Koko Tariq A. Khan M. Qaiser Fatmi Mahrukh Imtiaz Riaz A. Khan Hamdoon A. Mohammed Mariusz Jaremko Abdul-Hamid Emwas Faizul Azam Avinash D. Bholay Gamal O. Elhassan Dinesh K. Prajapati <i>In Vitro</i> and <i>In Silico</i> Approaches for the Antileishmanial Activity Evaluations of Actinomycins Isolated from Novel <i>Streptomyces smyrnaeus</i> Strain UKAQ_23 Antibiotics actinomycin X<sub>2</sub> actinomycin D <i>in silico</i> molecular modeling Kala-azar leishmaniasis molecular dynamics simulation |
author_facet |
Kamal A. Qureshi Ibrahim Al Nasr Waleed S. Koko Tariq A. Khan M. Qaiser Fatmi Mahrukh Imtiaz Riaz A. Khan Hamdoon A. Mohammed Mariusz Jaremko Abdul-Hamid Emwas Faizul Azam Avinash D. Bholay Gamal O. Elhassan Dinesh K. Prajapati |
author_sort |
Kamal A. Qureshi |
title |
<i>In Vitro</i> and <i>In Silico</i> Approaches for the Antileishmanial Activity Evaluations of Actinomycins Isolated from Novel <i>Streptomyces smyrnaeus</i> Strain UKAQ_23 |
title_short |
<i>In Vitro</i> and <i>In Silico</i> Approaches for the Antileishmanial Activity Evaluations of Actinomycins Isolated from Novel <i>Streptomyces smyrnaeus</i> Strain UKAQ_23 |
title_full |
<i>In Vitro</i> and <i>In Silico</i> Approaches for the Antileishmanial Activity Evaluations of Actinomycins Isolated from Novel <i>Streptomyces smyrnaeus</i> Strain UKAQ_23 |
title_fullStr |
<i>In Vitro</i> and <i>In Silico</i> Approaches for the Antileishmanial Activity Evaluations of Actinomycins Isolated from Novel <i>Streptomyces smyrnaeus</i> Strain UKAQ_23 |
title_full_unstemmed |
<i>In Vitro</i> and <i>In Silico</i> Approaches for the Antileishmanial Activity Evaluations of Actinomycins Isolated from Novel <i>Streptomyces smyrnaeus</i> Strain UKAQ_23 |
title_sort |
<i>in vitro</i> and <i>in silico</i> approaches for the antileishmanial activity evaluations of actinomycins isolated from novel <i>streptomyces smyrnaeus</i> strain ukaq_23 |
publisher |
MDPI AG |
series |
Antibiotics |
issn |
2079-6382 |
publishDate |
2021-07-01 |
description |
Leishmaniasis, a Neglected Tropical Parasitic Disease (NTPD), is induced by several <i>Leishmania</i> species and is disseminated through sandfly (<i>Lutzomyia longipalpis</i>) bites. The parasite has developed resistance to currently prescribed antileishmanial drugs, and it has become pertinent to the search for new antileishmanial agents. The current study aimed to investigate the <i>in vitro</i> and <i>in silico</i> antileishmanial activity of two newly sourced actinomycins, X<sub>2</sub> and D, produced by the novel <i>Streptomyces smyrnaeus</i> strain UKAQ_23. The antileishmanial activity conducted on promastigotes and amastigotes of <i>Leishmania major</i> showed actinomycin X<sub>2</sub> having half-maximal effective concentrations (EC<sub>50</sub>), at 2.10 ± 0.10 μg/mL and 0.10 ± 0.0 μg/mL, and selectivity index (SI) values of 0.048 and 1, respectively, while the actinomycin D exhibited EC<sub>50</sub> at 1.90 ± 0.10 μg/mL and 0.10 ± 0.0 μg/mL, and SI values of 0.052 and 1. The molecular docking studies demonstrated squalene synthase as the most favorable antileishmanial target protein for both the actinomycins X<sub>2</sub> and D, while the xanthine phosphoribosyltransferase was the least favorable target protein. The molecular dynamics simulations confirmed that both the actinomycins remained stable in the binding pocket during the simulations. Furthermore, the MMPBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) binding energy calculations established that the actinomycin X<sub>2</sub> is a better binder than the actinomycin D. In conclusion, both actinomycins X<sub>2</sub> and D from <i>Streptomyces smyrnaeus</i> strain UKAQ_23 are promising antileishmanial drug candidates and have strong potential to be used for treating the currently drug-resistant leishmaniasis. |
topic |
actinomycin X<sub>2</sub> actinomycin D <i>in silico</i> molecular modeling Kala-azar leishmaniasis molecular dynamics simulation |
url |
https://www.mdpi.com/2079-6382/10/8/887 |
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