Spodoptera litura Fab. (Lepidoptera, Noctuidae) is a polyphagous pest and has been shown to be resistant to a wide range of insecticides, which has led to sporadic out breaks of the pest and failure of crops. We were interested to establish if resistance to insecticides is diverse in different populations of S. litura collected from various areas with variable temperatures. We collected S. litura from eight different locations and compare the toxicity of insecticides. Resistance to the pyrethroids ranged from 20-to 11,700-fold compared with the Lab-PK (laboratory susceptible population). The resistance to bifenthrin was the lowest in a population collected from Multan and the highest to esfenvalerate in a population collected from Lodhran. Similarly, very high level of resistance to spinosad, indoxacarb, and methoxyfenozide was observed in all eight populations. In contrast, resistance to organophosphates was significantly lower than the pyrethroids, spinosad, indoxacarb, and methoxyfenozide, while toxicity of emamectin to field populations was similar to the LabPk. The results are discussed in relation to integrated pest management (IPM) for S. litura with special reference to management of field evolved resistance to insecticides.

Background: ATP-binding cassette super family G2 protein is an active ATP-binding cassette transporter with potential to combat cancer stem cells. Objective: Due to the lack of potential ATP-binding cassette super family G2 inhibitors we screened natural inhibitors, which could be safe source to control multidrug resistance by blocking the regulation of ATP-binding cassette super family G2 protein. Method: Three-dimensional structure of ATP-binding cassette super family G2 protein downloaded from the protein databank and chemical structures of selected 166 compounds of the training dataset retrieved from PubChem. Drug-likeness and docking analysis shortlisted the dataset for pharmacophore generation. LigandScout 4.1.5 used for pharmacophore-based screening of Zbc library of ZINC database and Autodock Vina utilized for molecular docking against the predicted active pocket of the target protein to evaluate potential association of protein and ligands. Physiochemical properties of novel compounds calculated by admetSAR respectively. Results: Through pharmacophore-based screening, ZINC4098704 (Rhein) was identified as a lead compound which demonstrates least binding energy (-8.5) and highest binding affinity with the target protein and showed optimal physiochemical profile. This compound is highly recommended for laboratory test to confirm its activity as ATP-binding cassette super family G2 inhibitors. Conclusion: Our computer-based study systematically selected natural lead compound, which could be effective in inhibiting ATP-binding cassette super family G2 and may be helpful in reversing the effect of multidrug resistance in order to increase the effectiveness of chemotherapy in cancer treatment.

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IntroductionIt is a known fact that Breast cancer is a known universal disease, with an annual prevalence of 1.3 million cases each year, accounts for more than 23 diseases among all malignancies Breast cancer is more common. In spite of major advances and treatments in its early detection, breast carcinoma still remains a significant reason for morbidity and mortality of women around the world [1]. Breast cancer is the second leading reason behind the death of most females. The most common measure of the treatment of breast cancer is surgery typically followed by adjuvant radiation, chemotherapy, and endocrine therapy, but in a few cases, only medication is given along with radiotherapy [2]. About 70% of breast cancers express mutations in estrogen receptor (ER), while most of the breast cancers demonstrate sensitivity to the inhibition of ER. However, due to unknown facts and reasons, several tumors become unmanageable to ER inhibition during metastatic breast cancer [3].Estrogen receptors are the member of the nuclear receptor family, thus tend to act as a ligand-activated transcription factors. The binding of ligand prompts a conformational change in the receptor, which results in its translocation into the nucleus, thus activates transcription of several target genes [4]. Mutations of Esterogen Receptor (ESR1) affect its ligand-binding domain. ESR1 are a key mechanism in accomplishing endocrine resistance in breast carcinoma therapy. The ordinary mutations occur in ER Ligand binding domain results in mutations of Tyrosine/Serionine/Aspargin 537, Asp 538, Glycine, Glutamine, Leucine 536, Methionine 543, Leucine 544 and Aspartic acid 531 amino acid residues [5]. Hormone therapy is usually accustomed to inhibit estrogen receptor signal or block ER production. It is at first effective within the roughly seventy percent of patients with breast carcinoma, who have ER-positive tumors; however, several Abstract Background: Mutations of Estrogen receptors 1 affect its ligand-binding domain and results in the formation of breast cancer. Breast cancer is a known universal disease and the second leading reason behind the death of most females. About 70% of breast cancers express the estrogen receptor. This study was undertaken to realize perceptions into molecular mechanisms and structural necessities that are crucial for potential inhibition of ESR1. Methods:In this research ESR1 proteins were selected and pharmacophore models were generated, virtual screening was done to obtain hit compounds against reference shared feature pharmacophore, the hit compounds were docked with ESR1 proteins. Results:The pharmacophore displayed three main features Hydrogen bond acceptor, Hydrogen bond donor and aromatic rings. 10 hit compounds were obtained by virtual screening; compounds were further sorted for Lipinski rule of five before docking. Compounds that fulfill all properties of Lipinski rule of five were docked with proteins, 3 compounds demonstrated ideal docking results. They fit appropriately in the pocket of proteins which ...

The authors have proposed a systems theory-based novel drug design approach for the p53 pathway. The pathway is taken as a dynamic system represented by ordinary differential equations-based mathematical model. Using control engineering practices, the system analysis and subsequent controller design is performed for the re-activation of wild-type p53. p53 revival is discussed for both modes of operation, i.e. the sustained and oscillatory. To define the problem in control system paradigm, modification in the existing mathematical model is performed to incorporate the effect of Nutlin. Attractor point analysis is carried out to select the suitable domain of attraction. A two-loop negative feedback control strategy is devised to drag the system trajectories to the attractor point and to regulate cellular concentration of Nutlin, respectively. An integrated framework is constituted to incorporate the pharmacokinetic effects of Nutlin in the cancerous cells. Bifurcation analysis is also performed on the p53 model to see the conditions for p53 oscillation.