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INNOSC Theranostics and
Pharmacological Sciences Docking study of quinoline-3-carbaldehyde derives

3.2. Toxicity results of compound (5), hypothetical Notably, compound 5 and forty-one of the hypothetical
compounds (A1–A50), and ten antimalarial derivatives exhibited failures in one or more of these tests,
reference drugs suggesting potential toxic and carcinogenic activities .
[22]
A total of 50 hypothetical compounds (A1–A50) depicted However, nine lead compounds (A5, A20, A31, A33, A34,
in Figure 5, along with ten reference drugs (artesunate, A36, A45, A48, and A49) shown in Figure 3 demonstrated
doxycycline, tafenoquine, amodiaquine, arthemeter, full compliance with the evaluated toxicity parameters
lumefantrine, primaquine, piperaquine, mefloquine, and (Tables 1 and 2).
chloroquine), were subjected to virtual investigations Notably, the toxicity results for the reference drugs, as
to evaluate their toxicity profiles. The specific shown in Tables 3 and 4, revealed that only mefloquine
toxicity parameters examined included hepatoxicity, demonstrated compliance with the evaluated parameters.
carcinogenicity, immunogenicity, mutagenicity, and In contrast, the other reference drugs exhibited one or more
cytotoxicity, as outlined in Table 1. violations when compared to the nine lead compounds.

Table 3. Toxicity prediction of standard drugs against P. falciparum using Protox II webserver
Target Mefloquine Piperaquine Artesunate Doxycycline Tafenoquine
Hepatotoxicity Inactive (0.75) Inactive (0.78) Inactive (0.76) Active (0.54) Inactive (0.78)
Carcinogenicity Active (0.76) Inactive (0.71) Inactive (0.65) Inactive (0.77) Inactive (0.63)
Immunotoxicity Inactive (0.84) Active (0.93) Active (0.87) Active (0.99) Active (0.99)
Mutagenicity Inactive (0.68) Active (0.50) Inactive (0.63) Inactive (0.95) Active (0.54)
Cytotoxicity Inactive (0.74) Inactive (0.82) Inactive (0.87) Inactive (0.90) Inactive (0.63)

Table 4. Toxicity prediction of standard drugs against P. falciparum using Protox II webserver
Target Amodiaquine Artemether Lumefantrine Primaquine Chloroquine
Hepatotoxicity Inactive (0.61) Inactive (0.77) Inactive (0.70) Inactive (0.84) Inactive (0.90)
Carcinogenicity Active (0.61) Inactive (0.66) Inactive (0.61) Inactive (0.59) Inactive (0.66)
Immunotoxicity Active (0.99) Active (0.92) Active (0.99) Active (0.99) Active (0.69)
Mutagenicity Inactive (0.75) Inactive (0.60) Inactive (0.60) Active (0.79) Active (0.94)
Cytotoxicity Inactive (0.53) Inactive (0.94) Inactive (0.67) Inactive (0.61) Inactive (0.93)

Table 5. Physicochemical properties and drug‑likeness of lead compounds using SwissADME webserver
Physico* 5 A5 A31 A36 A20 A33 A34 A45 A48 A49 Mefloq
MW 367.40 381.42 449.42 427.51 383.40 409.48 409.48 429.49 383.40 383.40 378.31
#rot_b 5 5 6 7 5 6 6 6 5 5 4
#HA 4 4 7 4 5 4 4 5 5 5 9
#HD 0 0 0 0 1 0 0 0 1 1 2
TPSA 56.26 56.26 56.26 81.56 76.49 56.26 56.26 104.29 76.49 76.49 45.15
natoms 28 29 33 31 29 31 31 31 29 29 26
nviol 1 1 1 1 1 1 1 1 1 1 2
log Kp −4.83 −4.66 −4.45 −4.58 −5.18 −4.29 −4.29 −5.13 −4.79 −5.18 −6.04
Bioav 0.55 0.55 0.55 0.55 0.55 0.55 0.55 0.55 0.55 0.55 0.55
GI High High Low Low High High High Low High High High
BBB Yes No No No No No No No No No No
Pgp No No Yes Yes No Yes Yes No No No Yes
Abbreviations: TPSA: Total polar surface area; natoms: Number of atoms in the molecule; MW: Molecular weight; #HA: Number of hydrogen bond
acceptors; #HD: Number of hydrogen bond donors; nviol: Number of violations; #rot_b: Number of rotatable bonds; bioav: Bioavailability;
GI: Gastrointestinal absorption; BBB: Blood–brain barrier; Pgp: Permeability glycoprotein substrate; Mefloq: Mefloquine.

Volume 7 Issue 1 (2024) 8 https://doi.org/10.36922/itps.0976