Lead Application to Cure Sap Wells by Deploying Straddle Packer, Success Story

Objective/Scope The Increase of inactive wells due to subsurface integrity issue is observed in brown fields, Fig-1 is, showing the record for onshore UAE asset, the economic challenges is calling for alternative solutions to restore well integrity with lower cost. Straddle packer application is consists of two tandom packers with spacer pipe in between with anchoring system deployed riglessly in the well to isolate the communication point between Ann A and Tubing.Fig-2, Methods, Procedures, Process Communication between tubing and annulus A (Failure of primary barrier) is identified as the right candidate wells for straddle packer application, First step is to clearly identify the point of communication, it has been done by annulus pressure investigation excersize during flowing and shut in condition, observing the return of annulus fluid which was the same produced gas Noise log has been conducted and clearly identified the communication point at SPM (Side Pocket Mandrel) to be used for emergency killing, Tubing integrity test was conducted using nippless plugs and inflow test below and above the leak point and confirm no other leak points within the tubing Engineering drawing for the leaking assembly was reviewed to design the dimension of straddle packer assembly, length and packer size It is recommended to deploy the assembly using electric line correlation for accurate depth selection After setting annulus pressure observed no build up Well opened safely to production Results/Observation/Conclusion Leak point arrested, well primary barrier restored Removed from DWS (drilling and workover schedule) and restore well production in addition to improving inactive string KPI for Gas asset Save almost work over cost for gas well XX-197 Novel/ Additive information The way forward is to check the scalability of extending this application among other ADNOC assets and to screen the right candidate wells for this application To add this application as a part of well integrity procedures and recommendations for such like cases

Artificial Lift Rigless Opportunity to Re-Activate the Inactive Wells Inventory an a Middle East Mega-Field After a Successful Pilot of a Best Practices and New Technology With Jet Pump

A Gulf oil operation company has been working to evaluate a rigless method of Artificial Lift System (ALS) suitable for its current assets and any future needs on ALS to minimize the impact of deferred production, and having the flexibility to bringing back the inactive string to production and act as a sustained production lift method. This paper describes a comprehensive study of the main objectives for a rigless Artificial Lift trial. The Rigless Jet Pump system was selected as one of the ALS fast implementation methods to activate the inactive wells. The trial was conducted in two inactive wells; across two different mega-fields, enabling both wells to produce stably and continuously with an average production rate of 650 BOPD. A thorough assessment was performed and the Rigless Jet Pump System was declared as a successful pilot providing confidence to scale up across all the company fields. The scale-up plans it will include 10 systems that can be rotated and applied where needed across all company fields. The trial implementation of the Rigless Jet Pump was evaluated based on supply and the connectivity in the field. This includes equipment mobilization (from the call-out time), availability of the field resources, the installation job, and up to the Surface Equipment connectivity plan. The evaluation also closely monitored the subsequence rig-up procedure and rigless deployment of the downhole equipment which was designed for installation straddled across an existing gas lift side pocket mandrel. Once surface and subsurface installation was completed, the wells were put on production to reactivate the inactive strings. Both wells were tested to confirm the achievement of a minimum of 80% of the designed production rates. The performance of the rigless activation of inactive wells using a jet pump has been proven successful. Both wells showed promising results while jet pump operation confirming a profitable alternative to accelerate production across fields toward achieving production mandates. The performance of the system delivered the Efficiency and Safety (HSE & Integrity) expected as part of the project KPI's. This novel practice for the Jet Pump System is linked to the rigless deployment and retrieval mechanism with topside equipment skid mounted for easy movement to other wells. This gives to the oil field operators an alternative and competitive edge over other modes of lift that required a workover program. The rigless method can be adapted to the existing in-active wells with SPM (side Pocket Mandrels) or without; by a tubing punch after a comprehensive integrity evaluation.

Design, Synthesis, Biological Evaluation, and Computational Studies of Novel Tri-Aryl Imidazole-Benzene Sulfonamide Hybrids as Promising Selective Carbonic Anhydrase IX and XII Inhibitors

A novel series of tri-aryl imidazole derivatives 5a–n carrying benzene sulfonamide moiety has been designed for their selective inhibitory against hCA IX and XII activity. Six compounds were found to be potent and selective CA IX inhibitors with the order of 5g > 5b > 5d > 5e > 5g > 5n (Ki = 0.3–1.3 μM, and selectivity ratio for hCA IX over hCA XII = 5–12) relative to acetazolamide (Ki = 0.03 μM, and selectivity ratio for hCA IX over hCA XII = 0.20). The previous sixth inhibitors have been further investigated for their anti-proliferative activity against four different cancer cell lines using MTT assay. Compounds 5g and 5b demonstrated higher antiproliferative activity than other tested compounds (with GI50 = 2.3 and 2.8 M, respectively) in comparison to doxorubicin (GI50 = 1.1 M). Docking studies of these two compounds adopted orientation and binding interactions with a higher liability to enter the active side pocket CA-IX selectively similar to that of ligand 9FK. Molecular modelling simulation showed good agreement with the acquired biological evaluation.

Structural Insights into the Interactions of Digoxin and Na+/K+-ATPase and Other Targets for the Inhibition of Cancer Cell Proliferation

Digoxin is a cardiac glycoside long used to treat congestive heart failure and found recently to show antitumor potential. The hydroxy groups connected at the C-12, C-14, and C-3′a positions; the C-17 unsaturated lactone unit; the conformation of the steroid core; and the C-3 saccharide moiety have been demonstrated as being important for digoxin’s cytotoxicity and interactions with Na+/K+-ATPase. The docking profiles for digoxin and several derivatives and Na+/K+-ATPase were investigated; an additional small Asn130 side pocket was revealed, which could be useful in the design of novel digoxin-like antitumor agents. In addition, the docking scores for digoxin and its derivatives were found to correlate with their cytotoxicity, indicating a potential use of these values in the prediction of the cancer cell cytotoxicity of other cardiac glycosides. Moreover, in these docking studies, digoxin was found to bind to FIH-1 and NF-κB but not HDAC, IAP, and PI3K, suggesting that this cardiac glycoside directly targets FIH-1, Na+/K+-ATPase, and NF-κB to mediate its antitumor potential. Differentially, digoxigenin, the aglycon of digoxin, binds to HDAC and PI3K, but not FIH-1, IAP, Na+/K+-ATPase, and NF-κB, indicating that this compound may target tumor autophagy and metabolism to mediate its antitumor propensity.

Pharmacoinformatics based elucidation and designing of potential inhibitors against Plasmodium falciparum to target importin α/β mediated nuclear importation

Plasmodium falciparum, the prime causative agent of malaria, is responsible for 4, 05,000 deaths per year and fatality rates are higher among the children aged below 5 years. The emerging distribution of the multi-drug resistant P. falciparum becomes a worldwide concern, so the identification of unique targets and novel inhibitors is a prime need now. In the present study, we have employed pharmacoinformatics approaches to analyze 265 lead-like compounds from PubChem databases for virtual screening. Thereafter, 15 lead-like compounds were docked within the active side pocket of importin alpha. Comparative ligand properties and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profile were also assessed. Finally, a novel inhibitor was designed and assessed computationally for its efficacy. From the comparative analysis we have found that our screened compounds possess better results than the existing lead ivermectin; having the highest binding energy of −15.6 kcal/mol, whereas ivermectin has −12.4kcal/mol. The novel lead compound possessed more fascinating output without deviating any of the rules of Lipinski. It also possessed higher bioavailability and the drug-likeness score of 0.55 and 0.71, respectively compared to ivermectin. Furthermore, the binding study was confirmed by molecular dynamics simulation over 25 ns by evaluating the stability of the complex. Finally, all the screened compounds and the novel compound showed promising ADMET properties likewise. To end, we hope that our proposed screened compounds, as well as the novel compound, might give some advances to treat malaria efficiently in vitro and in vivo.

Mobile loop dynamics in adenosyltransferase control binding and reactivity of coenzyme B12

Cobalamin is a complex organometallic cofactor that is processed and targeted via a network of chaperones to its dependent enzymes. AdoCbl (5′-deoxyadenosylcobalamin) is synthesized from cob(II)alamin in a reductive adenosylation reaction catalyzed by adenosyltransferase (ATR), which also serves as an escort, delivering AdoCbl to methylmalonyl-CoA mutase (MCM). The mechanism by which ATR signals that its cofactor cargo is ready (AdoCbl) or not [cob(II)alamin] for transfer to MCM, is not known. In this study, we have obtained crystallographic snapshots that reveal ligand-induced ordering of the N terminus ofMycobacterium tuberculosisATR, which organizes a dynamic cobalamin binding site and exerts exquisite control over coordination geometry, reactivity, and solvent accessibility. Cob(II)alamin binds with its dimethylbenzimidazole tail splayed into a side pocket and its corrin ring buried. The cosubstrate, ATP, enforces a four-coordinate cob(II)alamin geometry, facilitating the unfavorable reduction to cob(I)alamin. The binding mode for AdoCbl is notably different from that of cob(II)alamin, with the dimethylbenzimidazole tail tucked under the corrin ring, displacing the N terminus of ATR, which is disordered. In this solvent-exposed conformation, AdoCbl undergoes facile transfer to MCM. The importance of the tail in cofactor handover from ATR to MCM is revealed by the failure of 5′-deoxyadenosylcobinamide, lacking the tail, to transfer. In the absence of MCM, ATR induces a sacrificial cobalt–carbon bond homolysis reaction in an unusual reversal of the heterolytic chemistry that was deployed to make the same bond. The data support an important role for the dimethylbenzimidazole tail in moving the cobalamin cofactor between active sites.