Triterpenic and monoterpenic esters from stems of Ichnocarpus frutescens and their drug likeness potential

Abstract

Phytochemical studies of ethanolic extract of stems of Ichnocarpus frutescens resulted in the isolation of tetracyclic triterpenic ester lanosteryl oleate (6), two new monoterpenic esters, menth-1(7)-en-9-olyl dodecanoate (7), and 2-(4-methylcyclohex-3-enyl)propyl dodecanoate (8). Their structures were established on the basis of extensive spectral data analysis and chemical methods. From the literature survey, it was revealed that none of these three compounds have been reported earlier from any other parts of I. fructescens. Using StarDrop, drug metabolism and pharmacokinetic parameters have been studied, while data of toxicological endpoints were generated usingDerek Nexus. 7 is metabolically stable as compared to 6 and 8. All three molecules are highly lipophilic so tendency to get distributed in brain and adipose tissue is more. Based on the current knowledge database, Derek Nexus predicted that these molecules are not mutagenic, carcinogenic, genotoxic, hepatotoxic, hERG channel inhibitor, nephrotoxic, neurotoxic but StarDrop found them as probable developmental toxic. So in a word, these phytoconstituents have drug-likeness potential and can be evaluated for possible targets.

In Silico Studies Revealed Multiple Neurological Targets for the Antidepressant Molecule Ursolic Acid

“…Various parameters, which were included in the ADMET studies, are LogS, logS @ pH7.4, LogP, LogD, 2C9 pKi, hERG pIC50, BBB log ([brain]:[blood]), BBB category, HIA category, P-gp category, 2D6 affinity category, PPB90 category as pharmacokinetic features and Mitochondrial dysfunction, Thyroid toxicity, Photoallergenicity, Skin sensitization, Occupational asthma, Respiratory sensitization, Developmental toxicity, Teratogenicity, Bradycardia, Adrenal gland toxicity, Blood in urine, Mutagenicity in vitro , Mutagenicity in vivo , Photomutagenicity in vitro , alpha-2-mu-Globulin nephropathy, Anaphylaxis, Bladder urothelial hyperplasia, Cardiotoxicity, Cerebral oedema, Chloracne, Cholinesterase inhibition, Cumulative effect on white cell count and immunology, Cyanide-type effects, High acute toxicity, Methaemoglobinaemia, Nephrotoxicity, Neurotoxicity, Oestrogenicity, Peroxisome proliferation, Phospholipidosis, Phototoxicity, Kidney disorders, Bone marrow toxicity, Splenotoxicity, Irritation (of the gastrointestinal tract), Irritation (of the respiratory tract), Irritation (of the skin), Lachrymation, HERG channel inhibition in vitro , Hepato- toxicity, Non specific genotoxicity in vitro , Non specific genotoxicity in vivo , Photo-induced non-specific geno- toxicity in vitro , Photo-induced non-specific genotoxicity in vivo , Chromosome damage in vitro , Chromosome damage in vivo , Photo-induced chromosome damage in vitro , Carcino- genicity, Photocarcinogenicity, Pulmonary toxicity, Uncoupler of oxidative phosphorylation, Irritation (of the eye), Testicular toxicity, Ocular toxicity, Kidney function-related toxicity, Bladder disorders and Urolithiasis as toxicological features [ 38 - 40 ]. Results are presented in Table 2 .…”

“…ADMET studies were performed using StarDrop software of Optibrium Ltd and integrated Derek Nexus module of LHASA Ltd [ 38 - 40 ]. UA was subjected for the ADMET profiling.…”

<strong>Pharmacokinetics and Toxicological Profiling of Surfactin A: An <em>In silico</em> Approach</strong>

“…[blood]), BBB category, HIA category, P-gp category, 2D6 affinity category, PPB90 category, developmental toxicological category and composite site lability of these molecules on 3A4 isoform of cytochrome P450 [5][6].…”

“…Derek Nexus module of LHASA Ltd. was used to calculate toxicological endpoints like carcinogenicity, photo-carcinogenicity, chromosome damage in vitro, chromosome damage in vivo, photo-induced chromosome damage in vitro, genotoxicity in vitro, genotoxicity in vivo, photogenotoxicity in vitro, photogenotoxicity in vivo, hepatotoxicity, irritation (of the eye), irritation (of the gastrointestinal tract), irritation (of the respiratory tract), irritation (of the skin), lachrymation, HERG channel inhibition in vitro, alpha-2-mu-globulin nephropathy, anaphylaxis, bladder urothelial hyperplasia, cardiotoxicity, cerebral oedema, chloracne, cholinesterase inhibition, cumulative effect on white cell count and immunology, cyanide-type effects, high acute toxicity, methaemoglobinaemia, nephrotoxicity, neurotoxicity, oestrogenicity, peroxisome proliferation, phospholipidosis, phototoxicity, pulmonary toxicity, uncoupler of oxidative phosphorylation, developmental toxicity, teratogenicity, testicular toxicity, ocular toxicity, mutagenicity in vitro, mutagenicity in vivo, photomutagenicity in vitro, thyroid toxicity, photoallergenicity, skin sensitization, occupational asthma and respiratory sensitization [5][6].…”