Reconnoitering imidazopyridazines as anticancer agents based on virtual modelling approach: quantitative structure activity relationship, molecular docking and molecular dynamics.

Cancer is an unimpeded growth of cells leading to metathesis of cancer and eventually spread throughout the body. PIM kinases are the members of the serine threonine kinase playing role in cancer progression, differentiation and proliferation. Till date there is no single drug targeting PIM-1 kinase in the market, that has made itself a target in limelight for the discover of new anticancer agents.

Machine learning facilitated structural activity relationship approach for the discovery of novel inhibitors targeting EGFR.

This research manuscript aims to find the most effective epidermal growth factor receptor (EGFR) inhibitors from millions of in house compounds through Machine Learning (ML) techniques. ML-based structure activity relationship (SAR) models were validated to predict biological activity of untested novel molecules. Six ML algorithms, including k nearest neighbour (KNN), decision tree (DT), Logistic Regression, support vector machine (SVM), multilinear regression (MLR), and random forest (RF), were used to build for activity prediction.

Evaluation of wound healing effect of (Lam.) Mull. Arg. by in silico multitargets directed for multiligand approach.

The healing of wound is a tightly-regulated cascade of events, involving interplay of enormous factors. Now a days, pain alleviation and faster wound healing have attracted considerable attention. Several natural compounds have played crucial role in this intriguing process.

Phyto-metabolomics of phlogacanthus thyrsiformis by using LC-ESI-QTOF-MS/MS and GC/QTOF-MS: Evaluation of antioxidant and enzyme inhibition potential of extracts.

Phlogacanthus thyrsiformis (P. thyrsiformis) is a non-conventional edible plant that has been used as a vegetable and as a traditional medicine to treat various diseases. This non-conventional edible plant is widespread in India, Yunnan-Chinese provinces, and Vietnam.

Benzimidazole-linked pyrazolo[1,5-a]pyrimidine conjugates: synthesis and detail evaluation as potential anticancer agents.

A library of benzimidazole briged pyrazolo[1,5-a]pyrimidine (6a-q) was designed, synthesized and subjected for evaluation for cytotoxic potential. Antiproliferative activity, ranging from 3.1-51.

Computational modelling strategies in exploring triazolopyridazine PIM1 kinase inhibitors as anticancer agents.

Background: PIM (Proviral Integration site for Moloney Murine Leukemia virus) kinases are members of the class of kinase family serine/ threonine kinases, which play a crucial role in cancer development. As there is no drug in the market against PIM-1, kinase has transpired as a budding and captivating target for discovering new anticancer agents targeting PIM-1 kinase.

Aim: The current research pondered the development of new PIM-1 kinase inhibitors by applying a ligand-based and structure-based drug discovery approach involving 3D QSAR, molecular docking, and dynamics simulation.

Topical advances in PIM kinases and their inhibitors: Medicinal chemistry perspectives.

Cytosolic PIM kinases are the members of serine/ threonine family play a crucial role in the cancer progression and development. Overexpression of PIM kinases is observed in various types of cancers including prostate, hematological, pancreatic, breast carcinoma and likewise. PIM kinases have now been considered as limelight target for the discovery of new molecules as novel anticancer agents as no drug is in the market targeting PIM kinases.

Synthesis and biological evaluation of chalcone-linked pyrazolo[1,5-]pyrimidines as potential anticancer agents.

A series of pyrazolo[1,5-]pyrimidines substituted at C5 with 1-phenylprop-2-en-1-one () and 3-phenylprop-2-en-1-one () was synthesized and evaluated for antiproliferative activity. Among them, was found to be the most active compound against the MDA-MB-231 cell line with an IC of 2.6 μM .

Design and synthesis of 1,2,3-triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates as tubulin polymerization inhibitors.

1,2,3-Triazolo linked benzo[d]imidazo[2,1-b]thiazole conjugates (5a-v) were designed, synthesized and evaluated for their cytotoxic potency against some human cancer cell lines like DU-145 (prostate), HeLa (cervical), MCF-7 (breast) HepG2 (liver) and A549 (lung). Preliminary results revealed that some of these conjugates like 5f and 5k exhibited significant antiproliferative effect against human breast cancer cells (MCF-7) with IC values of 0.60 and 0.

Synthesis and biological evaluation of cis-restricted triazole/tetrazole mimics of combretastatin-benzothiazole hybrids as tubulin polymerization inhibitors and apoptosis inducers.

A series of colchicine site binding tubulin inhibitors were synthesized by the modification of the combretastatin pharmacophore. The ring B was replaced by the pharmacologically relevant benzothiazole scaffolds, and the cis configuration of the olefinic bond was restricted by the incorporation of a triazole and tetrazole rings which is envisaged by the structural resemblance to a tubulin inhibitor like combretastatin (CA-4). These compounds were evaluated for their antiproliferative activity on selected cancer cell lines and an insight in the structure activity relationship was developed.

2-aryl benzimidazole conjugate induced apoptosis in human breast cancer MCF-7 cells through caspase independent pathway.

Apoptosis is a representative form of programmed cell death, which has been assumed to be critical for cancer prevention. Thus, any agent that can induce apoptosis may be useful for cancer treatment and apoptosis induction is arguably the most potent defense against cancer promotion. In our previous studies, 2-aryl benzimidazole conjugates were synthesized and evaluated for their antiproliferative activity and one of the new molecule (2f) was considered as a potential lead.

Synthesis and biological evaluation of imidazopyridinyl-1,3,4-oxadiazole conjugates as apoptosis inducers and topoisomerase IIα inhibitors.

A series of imidazopyridinyl-1,3,4-oxadiazole conjugates were synthesized and investigated for their cytotoxic activity and some compounds showed promising cytotoxic activity. Compound 8q (NSC: 763639) exhibited notable growth inhibition that satisfies threshold criteria at single dose (10μM) on all human cancer cell lines. This compound was further evaluated at five dose levels (0.

Investigation of the mechanism and apoptotic pathway induced by 4β cinnamido linked podophyllotoxins against human lung cancer cells A549.

Apoptosis is essential for normal development and the maintenance of homeostasis. It plays a necessary role to protect against carcinogenesis by eliminating damaged cells. Many studies have demonstrated that the dysregulation of apoptosis results in cancer and this provides an approach to develop therapeutic agents via inducing apoptosis.

Design and synthesis of dithiocarbamate linked β-carboline derivatives: DNA topoisomerase II inhibition with DNA binding and apoptosis inducing ability.

A series of new β-carboline-dithiocarbamate derivatives bearing phenyl, dithiocarbamate and H/methyl substitutions at position-1, 3 and 9, respectively, were designed and synthesized. These derivatives 8a-l and 13a-l and their starting precursors (7 a-d and 12 a-d) have been evaluated for their in vitro cytotoxic activity on selected human cancer cell lines. Among the derivatives tested, 7 c, 12 c, 8 a, 8 d, 8 i, 8 j, 8 k, 8l and 13 d-l exhibited considerable cytotoxicity against most of the tested cancer cell lines (IC50<10μM).

Synthesis and biological evaluation of benzo[d][1,3]dioxol-5-yl chalcones as antiproliferating agents.

A series of chalcone derivatives were designed, synthesized, and evaluated for their cytotoxic potential. These molecules have showed promising cytotoxic activity with IC50 values ranging from 5.24 to 63.

Synthesis of 2-anilinopyridyl-triazole conjugates as antimitotic agents.

A series of 2-anilinopyridyl–triazole conjugates (6a–t) were prepared and evaluated for their cytotoxic activity against a panel of three human cancer cell lines. Among them compounds 6q, 6r and 6s showed significant cytotoxic activity with IC50 values ranging from 0.1 to 4.

Synthesis of 2-anilinopyridine dimers as microtubule targeting and apoptosis inducing agents.

A series of 2-anilinopyridine dimers have been synthesized and evaluated for their anticancer potential. Most of the compounds have showed significant growth inhibition of the cell lines tested and compound 4d was most effective amongst the series displaying a GI50 of 0.99 μM specifically against the prostate cancer cell line (DU145).

Synthesis of β-carboline-benzimidazole conjugates using lanthanum nitrate as a catalyst and their biological evaluation.

A series of β-carboline-benzimidazole conjugates bearing a substituted benzimidazole and an aryl ring at C3 and C1 respectively were designed and synthesized. The key step of their preparation was determined to involve condensation of substituted o-phenylenediamines with 1-(substituted phenyl)-9H-pyrido[3,4-b]indole-3-carbaldehyde using La(NO3)3·6H2O as a catalyst and their cytotoxic potential was evaluated. Conjugates 5a, 5d, 5h and 5r showed enhanced cytotoxic activity (GI50 values range from 0.

Design and synthesis of C3-pyrazole/chalcone-linked beta-carboline hybrids: antitopoisomerase I, DNA-interactive, and apoptosis-inducing anticancer agents.

A series of β-carboline hybrids bearing a substituted phenyl and a chalcone/(N-acetyl)-pyrazole moiety at the C1 and C3 positions, respectively, was designed, synthesized, and evaluated for anticancer activity. These new hybrid molecules showed significant cytotoxic activity, with IC50 values ranging from <2.0 μM to 80 μM, and the structure-activity relationships (SAR) associated with substitutions at positions 1 and 3 of these hybrids was clearly addressed.

Synthesis and biological evaluation of new epalrestat analogues as aldose reductase inhibitors (ARIs).

Baylis-Hillman chemistry derived four series of new epalrestat analogues were synthesized. Three structural changes are introduced in these 39 new epalrestat analogues synthesized. All compounds were evaluated for their in vitro aldose reductase inhibitory (ALR) activity.

Anti-tubercular agents. Part 7: a new class of diarylpyrrole-oxazolidinone conjugates as antimycobacterial agents.

In an effort to discover new anti-tubercular agents, a series of new diarylpyrrole-oxazolidinone conjugates have been designed and synthesized. The anti-tubercular activity of these new conjugates (4a-n and 5a-d) against Mycobacterium tuberculosis H37Rv and drug resistance strains such as M. tuberculosis Rif(R) and M.

Divalent N(I) character in 2-(thiazol-2-yl)guanidine: an electronic structure analysis.

Several medicinally important compounds carry a 2-(thiazol-2-yl)guanidine unit. These species are generally (erroneously) represented as 1-(thiazol-2-yl)guanidine species. Quantum chemical studies were performed to identify the appropriate tautomeric state of this class of compounds.